Smallpox, also known as variola, is an acute, highly contagious infectious disease caused by the poxvirus variola. After a global eradication program, the World Health Organization pronounced smallpox eradicated on October 26, 1979, 2 years after the last naturally occurring case was reported in Somalia. Vaccination is no longer recommended, except for certain laboratory workers. The last known case in the United States was reported in 1949. Although naturally occurring smallpox has been eradicated, variola virus preserved in laboratories remains an unlikely source of infection. In response to bioterrorism concerns, smallpox vaccination was offered to members of the military, health department officials, first responders, and key health care providers. If a bioterrorism event involving smallpox is suspected or occurs, vaccination programs can be initiated.

Naturally occurring smallpox exists in two major forms: variola major (classic smallpox) and variola minor. Variola major is classified into four types—ordinary (accounts for 90% of cases), modified (a mild variant of smallpox that occurs in previously vaccinated people who have only partial immunity), flat, and hemorrhagic; the flat and hemorrhagic forms of variola are both rare and usually fatal. Variola minor is a mild form of smallpox that occurs in nonvaccinated people and results from a less virulent strain.

Smallpox can affect people of all ages. In the past, the incidence was highest during the winter months in temperate zones; in the tropics, it occurred primarily during the hot, dry months.