Heat is the primary weather-related cause of death in the United States. Increasing heat and humidity, at least partially related to anthropogenic climate change, suggest that a long-term increase in heat-related mortality could occur. We calculated the annual excess mortality on days when apparent temperatures--an index that combines air temperature and humidity--exceeded a threshold value for 28 major metropolitan areas in the United States from 1964 through 1998. Heat-related mortality rates declined significantly over time in 19 of the 28 cities. For the 28-city average, there were 41.0 +/- 4.8 (mean +/- SE) excess heat-related deaths per year (per standard million) in the 1960s and 1970s, 17.3 +/- 2.7 in the 1980s, and 10.5 +/- 2.0 in the 1990s. In the 1960s and 1970s, almost all study cities exhibited mortality significantly above normal on days with high apparent temperatures. During the 1980s, many cities, particularly those in the typically hot and humid southern United States, experienced no excess mortality. In the 1990s, this effect spread northward across interior cities. This systematic desensitization of the metropolitan populace to high heat and humidity over time can be attributed to a suite of technologic, infrastructural, and biophysical adaptations, including increased availability of air conditioning.