Death rates become progressively higher when outdoor air temperature rises above or falls below 20–25°C. This study addresses the question of whether this relation is largely attributable to the direct effects of exposure to heat and cold on the human body in general, and on the circulatory system in particular. The association between daily mortality and daily temperatures in the Nethetlands in the period 1979–1987 was examined by controlling for influenza incidence, air pollution, and season; distinguishing lag periods; examining effect modification by wind speed and relative humidity; and distinguishing causes of death. Important direct effects of exposure to cold and heat on mortality were suggested by the following findings: 1) control for influenza incidence reduced cold-related mortality by only 34% and reduced heat-related mortality by 23% (the role of air pollution and “season” was negligible); 2) 62% of the “unexplained” cold-related mortality, and all heat-related mortality, occurred within 1 week; and 3) effect modification by wind speed was in the expected direction. The finding that 57% of “unexplained” cold-related mortality and 26% of the “unexplained” heat-related mortality was attributable to cardiovascular diseases suggests that direct effects are only in part the result of increased stress on the circulatory system. For heat-related mortality, direct effects on the respiratory system are probably more important. For cold-related mortality, the analysis yielded evidence of an important indirect effect involving increased incidence of influenza and other respiratory infections.