Variola, or smallpox, is an acute, highly contagious infectious disease caused by the poxvirus variola. After a global eradication program, the World Health Organization pronounced it eradicated on October 26, 1979, 2 years after the last naturally occurring case was reported in Somalia. Vaccination is now being reconsidered in light of potential biological attacks. The Centers for Disease Control and Prevention is actively involved in plans for both pre-emptive and emergency vaccination.

Variola developed in three major forms: variola major (classic smallpox), which carried a high mortality; variola minor, a mild form that occurred in nonvaccinated people and resulted from a less virulent strain; and varioloid, a mild variant that occurred in previously vaccinated people who had only partial immunity.