Smallpox was a serious illness caused by the variola virus. It caused a severe rash that often left disfiguring scars. About 1 in 3 people who got smallpox died. Smallpox has been eradicated since 1980. There haven’t been any cases since 1978. Smallpox was the first disease for which there was a vaccine.


Photo shows large, fluid-filled blisters on the skin of someone with smallpox.
Smallpox caused a hard, blistering rash over most of your body that left disfiguring scars.

What is smallpox?

Smallpox was a serious illness that killed hundreds of millions before its eradication. It caused a hard, blistering rash that often led to disfiguring scars. About 1 in 3 people who got smallpox died from it.

Beginning in the 1960s, the World Health Organization (WHO) led efforts to stop the spread of smallpox worldwide. By vaccinating and controlling outbreaks, they rid the world of smallpox. It was eradicated in 1980. The last naturally occurring case was in 1977.

Does smallpox still exist?

Smallpox no longer exists in humans or spreads naturally. There haven’t been any cases of smallpox in the last 45 years. Two laboratories (one in the U.S. and one in Russia) have stocks of the virus that causes smallpox for research purposes only.

How did we eradicate smallpox?

Some factors that may have contributed to successfully eradicating smallpox include:

  • Only humans get smallpox. It doesn’t spread through animals or insects. This means fewer ways to get infected.
  • It was easy to identify. Everyone who had smallpox had symptoms, including a characteristic rash. No one carried smallpox without knowing it (no asymptomatic carriers).
  • It spread relatively slowly. Smallpox usually wasn’t contagious until an infected person was too sick to be around many other people. It typically spread among people living in the same house.
  • Ring vaccination contained outbreaks. Because it spread only among close contacts, health officials could contain smallpox outbreaks with “ring vaccinations.” This meant vaccinating just those who had been around an infected person recently (a “ring” of contacts).
  • It had been around for thousands of years.Survivors of smallpox already had immunity. This meant that fewer people needed to be vaccinated to stop the spread.

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Symptoms and Causes

What are the symptoms of smallpox?

Symptoms of smallpox come in stages and include:

  • High fever.
  • Severe headache.
  • Backache.
  • Stomach pain.
  • Extreme fatigue and weakness.
  • Vomiting.
  • Rash that starts in your mouth and spreads to your face, then to the rest of your body.
  • Sores, then hard pustules that form from the rash.

Symptoms like fever, headache and fatigue appear first. They last two to four days, though the fever may continue or come back after the rash appears. The rash then goes through stages that each last several days.

What does a smallpox rash look like?

The smallpox rash starts in your mouth and on your face and quickly covers most of your body. It starts as a rash and ends up as hard bumps that turn into scabs. In the most common type of smallpox (ordinary smallpox), the rash goes through several stages:

  1. Early rash. After your initial symptoms, a rash develops on your tongue and the insides of your mouth and throat. Red spots in your mouth become sores, which break open.
  2. Spreading rash. The rash spreads to your face and then your arms, legs, back and torso. In about a day, it spreads all over your body, including the palms of your hands and the soles of your feet.
  3. Bumps on your skin fill with pus (thick fluid). There may be a dent in the middle of each bump. It takes about two days for the bumps to fill with fluid.
  4. Pustular rash and scabs. Bumps turn into pustules (firm, round lumps). Over the next 10 days, crusty scabs form over the pustules.
  5. Scabs resolve.Over about a week, the scabs fall off, leaving scars.


There are a few types of smallpox that cause slightly different symptoms:

  • Ordinary smallpox. Ordinary smallpox was the most common type of smallpox and caused the symptoms described above. It caused about 85% of cases. About 1 in 3 people with ordinary smallpox died.
  • Modified-type smallpox. People who had been vaccinated sometimes got modified-type smallpox. This was similar to ordinary smallpox, but the rash was less severe and didn’t last as long. Most people survived modified-type smallpox.
  • Flat-type (malignant) smallpox. Flat-type smallpox caused more severe initial symptoms than ordinary smallpox. The bumps from the rash merged together and never got hard or fluid-filled. This made a flat, soft rash that didn’t form scabs. Flat-type smallpox happened more often in children. It was almost always fatal.
  • Hemorrhagic smallpox. Hemorrhagic smallpox was more common in pregnant people. It caused severe initial symptoms. The rash usually didn’t get hard and fluid-filled. Instead, the skin underneath it bled, causing it to look black or burnt. It also caused internal bleeding and organ failure. Hemorrhagic smallpox was almost always fatal.

What causes smallpox?

The variola virus causes smallpox. There are two variants of variola: variola major and variola minor (or variola alastrim). Variola major caused most cases of smallpox and the most deaths. Variola minor caused similar, but less severe, symptoms. It was only fatal in 1% of cases, compared to over 30% of cases of variola major.

How did smallpox spread?

Smallpox spread through close, face-to-face contact. For instance, someone with smallpox could transmit it by coughing or talking to someone nearby. It was also possible to spread it through contact with infected items (like bedsheets or clothing).

What were the complications of smallpox?

Severe scarring was the most common complication of smallpox. Other complications included:

Why was smallpox so fatal?

While experts aren’t certain how smallpox caused death, it was likely a combination of factors, including:



Do we still vaccinate for smallpox?

Providers no longer regularly vaccinate against smallpox. Select groups of people — like some researchers and certain military personnel — are still vaccinated against smallpox. The U.S. government keeps stockpiles of smallpox vaccines, in case there’s another outbreak.

What year did the U.S. stop giving the smallpox vaccine?

In the U.S., providers stopped giving routine smallpox vaccinations in 1972. The last outbreak of smallpox in the U.S. was in 1949.

Does the smallpox vaccine last a lifetime?

Some studies suggest that the smallpox vaccine can provide protection for decades. For those who need a smallpox vaccination for their job, the Centers for Disease Control and Prevention (CDC) recommends getting a booster every three years.

Was smallpox the first disease to have a vaccine?

Yes. In the late 18th century, physician Edward Jenner confirmed long-told stories about dairymaids who were exposed to cowpox becoming immune to smallpox. We now know that cowpox and smallpox are very similar viruses. So, by getting cowpox, a minor illness, and becoming immune to it, people also became immune to smallpox.

Jenner began infecting people with cowpox to prevent them from getting smallpox, creating the first vaccine. The word “vaccine” is actually from the Latin word for cow (“vacca”).

Today, the smallpox vaccine is made from vaccinia, a virus similar enough to smallpox to provide immunity without getting you sick with smallpox.

What is variolation?

Variolation was an early form of vaccination. People would come in contact with the variola virus to purposefully get smallpox. They’d do this by either scratching their skin with the pus from smallpox sores or breathing in a powder made from the scabs. The illness they got from variolation was less severe than getting smallpox naturally, and they were then immune to smallpox. This practice is thought to date back hundreds of years.

Why does the smallpox vaccine leave a scar?

Unlike other modern vaccines, smallpox vaccines use a live, unaltered virus that’s similar to smallpox (called vaccinia). Instead of getting a shot, a healthcare provider dips a two-pronged needle into the virus and pricks your shoulder. You become infected with vaccinia at the vaccine site. The infection causes a blister to form, which later leaves a scar.

People who receive this kind of smallpox vaccine must follow directions for caring for the vaccination site carefully. If they don’t, they can infect someone else with vaccinia. Types of this vaccine include ACAM2000® and APSV.

The JYNNEOST™ vaccine, which is also used for mpox, uses an attenuated (weakened) virus and a more traditional shot. It has a lower risk of side effects than other smallpox vaccines. Healthcare providers give it in two shots under your skin, four weeks apart.

Additional Common Questions

Are there treatments for smallpox?

There are a few antiviral medications approved for smallpox. They include:

They were developed after smallpox was eradicated, so they’ve not been tested in people with a smallpox infection. But based on other kinds of testing, experts think they could be an option to treat smallpox if there’s another outbreak. They’ve been tested for safety in humans.

How was smallpox diagnosed?

Providers used the appearance of your rash and pattern of symptoms to diagnose smallpox. Providers can also test samples of your blood or tissue from your skin. They send the samples to a lab to look for viral DNA or antibodies to smallpox. The last diagnosed case of smallpox was in 1978.

What’s the difference between smallpox, mpox and chickenpox?

The viruses that cause smallpox and mpox both belong to the same genus (grouping) of viruses called orthopoxvirus. They share similar features, but mpox causes less severe illness than smallpox. Vaccination with vaccinia can provide protection against both.

Despite the word “pox” in the name, chickenpox is caused by a virus (varicella-zoster) that’s not related to smallpox or other orthopoxviruses.

A note from Cleveland Clinic

For centuries, smallpox was one of the world’s deadliest diseases. Today, most of us have never even had to think about it. No one has had smallpox in nearly half a century. And thanks to public health efforts, even in the unlikely event that there’s ever a future outbreak, the U.S. is prepared with treatments and vaccines.

Medically Reviewed

Last reviewed by a Cleveland Clinic medical professional on 04/07/2023.

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