The economic burden resulting from illness, disability, and premature death is of major importance in the allocation of health care resources and in the evaluation of health research and programs. This article updates the 1963 and 1972 studies of the costs of illness. In 1980, the estimated total economic costs of illness were $455 billion: $211 billion for direct costs, $68 billion for morbidity, and $176 billion for mortality. Diseases of the circulatory system and injuries and poisonings were the most costly, with variations in the diagnostic distributions among the three types of costs and by age and sex.