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The only infectious agent eradicated via vaccination

Symptoms and Causative Agent

Symptoms of a typical smallpox infection began with a fever and lethargy about two weeks after exposure to the Variola major virus. Headache, sore throat, and vomiting were also common. In a few days, a raised rash appeared on the face and body, and sores formed inside the mouth, throat, and nose. Fluid-filled pustules would develop and expand, in some cases joining together and covering large areas of skin. In about the third week of illness, scabs formed and separated from the skin.

The virus Variola minor caused a similar, though much less severe, form of smallpox.



Close contact spread smallpox with the sores or respiratory droplets of an infected person. Contaminated bedding or clothing could also spread the disease. A patient remained infectious until the last scab separated from the skin.


Complications and Mortality

About 30% of smallpox cases of the variola major type ended in death, typically in the second week of infection. Most survivors had some permanent scarring, which could be extensive. Other deformities could result, such as loss of lip, nose, and ear tissue. Blindness could occur due to corneal scarring. Variola minor was less severe and caused fewer of those infected to die.

Some estimates indicate that 20th century worldwide deaths from smallpox numbered more than 300 million.


Available Vaccines and Vaccination Campaigns

People have been using the smallpox vaccine since Edward Jenner first tested his idea that inoculation with matter from a cowpox sore would protect a person from smallpox. Jenner’s work eventually led to widespread production and commercialization of the smallpox vaccine.

Successful use of the smallpox vaccine led to the gradual reduction of smallpox cases. The last U.S. wild smallpox case occurred in 1949. After intensive vaccination campaigns in the 1960s and 1970s, the last case of wild smallpox in the world occurred in 1977.


U.S. Vaccination Recommendations

Routine vaccination against smallpox ended in the United States in the early 1970s, as its incidence lessened.

Certain U.S. military personnel and some civilian workers receive the smallpox vaccine due to the threat of bio-terrorism. The U.S. military uses a smallpox vaccine called ACAM2000, produced by Sanofi Pasteur. The virus in ACAM2000 is produced not on the flanks of cows, as with previous generations of vaccines, but in lab cultures of African green monkey cells.



  • Centers for Disease Control and Prevention. Emergency Preparedness and Response. Smallpox. Accessed 01/25/2018.
  • Center for Infectious Disease Research & Policy. U.S. military switching to new Smallpox vaccine. Accessed 01/25/2018.


Last update 9 April 2022