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Mortality trends of missionary staff serving in sub-Saharan Africa were tracked for the period 1945–1985. For 1945–1970, when more complete incidence data were available, the missionary death rate was approximately 40% lower, after adjustment, than would be expected in a comparable US population. This trend persisted through 1985. Between 1945 and 1970, the largest number of fatalities was attributable to malignancy, atherosclerosis, accidents, and infectious disease, and the greatest mortality risks, compared with the US experience, were from homicides, the complications of pregnancy, and infections, notably malaria, hepatitis, and polio. Beginning in the late 1950s, motor vehicle accidents became the leading cause of death. Since the 1960s, accidental causes of death have been approximately 50% higher than in the US, and homicides have been four times higher. During this same period, the infectious disease death rate decreased to approximately that within the US. Currently, the leading causes of mortality are motor vehicle accidents, malignancy, and atherosclerosis, followed by other accidental causes, notably aircraft mishaps and drownings. Viral hepatitis is presently the leading infectious disease cause of death. Other contemporary lethal infections include malaria, rabies, typhoid, Lassa fever, and retroviral infection. It was concluded that missionaries in sub-Saharan Africa had a death rate approximately half that expected in a comparable domestic control population. Preventive strategies, particularly relative to accident and infectious disease prevention, could effectively reduce mortality risk further.