The morbidity and mortality associated with the 1980 heat wave in St Louis and Kansas City, Mo, were assessed retrospectively. Heat-related illness and deaths were identified by review of death certificates and hospital, emergency room, and medical examiners' records in the two cities. Data from the July 1980 heat wave were compared with data from July 1978 and 1979, when there were no heat waves. Deaths from all causes in July 1980 increased by 57% and 64% in St Louis and Kansas City, respectively, but only 10% in the predominantly rural areas of Missouri. About one of every 1,000 residents of the two cities was hospitalized for or died of heat-related illness. Incidence rates (per 100,000) of heatstroke, defined as severe heat illness with documented hyperthermia, were 26.5 and 17.6 for St Louis and Kansas City, respectively. No heatstroke cases occurred in July 1979. Heatstroke rates were ten to 12 times higher for persons aged 65 years or older than for those younger than 65 years. The ratios of age-adjusted heatstroke rates were approximately 3:1 for nonwhite v white persons and about 6:1 for low v high socioeconomic status. Public health preventive measures in future heat waves should be directed toward the urban poor, the elderly, and persons of other-than-white races.