Data on monkeypox in Zaire over the five years 1980-1984 are analysed to assess the protection imparted by past smallpox vaccination and the transmission potential of the virus in unvaccinated communities. Attack rates in individuals with and without vaccination scars indicated that smallpox vaccination (discontinued in 1980) imparted approximately 85% protection against monkeypox. It is predicted that monkeypox virus will continue to be introduced into human communities from animal sources, and that the average magnitude and duration of monkeypox epidemics will increase as vaccine-derived protection declines in the population. On the other hand, current evidence indicates that the virus is appreciably less transmissible than was smallpox, and that it will not persist in human communities, even in the total absence of vaccination. The findings thus support the recommendation of the Global Commission for the Certification of Smallpox Eradication to cease routine smallpox vaccination in monkeypox endemic areas, but to encourage continued epidemiological surveillance.