mildly eruptive disease of cows that when transmitted to otherwise healthy humans produces immunity to smallpox. The cowpox virus is closely related to variola, the causative virus of smallpox. The word vaccinia is sometimes used interchangeably with cowpox to refer to the human form of the disease, sometimes to refer to the causative virus, and sometimes to refer only to the artificially induced human form of cowpox.

Cowpox disease, which is evident from the ulcers on the teats of cows, had been known as a disease of cows for hundreds of years; human cowpox occurred as a self-contained localized ulcer on the hands or at other sites where scratches or abrasions allowed entry of the virus. The preventive effect of vaccination, or intentional inoculation with the vaccinia virus, was demonstrated by Edward Jenner in 1796, following the observation that milkmaids who had been infected by cowpox during milking subsequently were immune to smallpox. During the 1980s, researchers discovered that rodents were also a natural reservoir for the virus, and that rodents, not cattle, were responsible for most cowpox infections in humans.

The vaccinia virus used in modern vaccines, though descended from cowpox, differs genetically from the existing cowpox virus; this difference may be a result of documented contamination of earlier vaccine cultures with variola virus, creating a hybrid that still confers immunity to smallpox infection. Vaccinia, by the strictest definition, does not occur in nature but enters the body during vaccination; though this usually produces a self-limiting, local ulcer like cowpox infection, it can cause a systemic smallpox-like disease in patients whose immunity is compromised, and it has—though rarely—been found to cause encephalitis.

With the disappearance of human smallpox by 1980, these risks have caused the discontinuation of routine vaccination on a population-wide basis.