Determining the possible adverse health effects of air pollutants can be complicated by differences in the environmental conditions of temperature and humidity. To evaluate the potentially confounding effects of differences in temperature and humidity, we exposed 8 normal male subjects and 8 male subjects with asthma to the extremes in temperature and humidity that could be maintained in an environmental chamber. We performed serial pulmonary function tests for these subjects before and during 6 hr exposure periods on 5 separate occasions: cold, dry (10°C, 10% relative humidity); cold, humid (10°C, 50% relative humidity); normal ambient (22°C, 40% relative humidity); hot, dry (37°C, 15% relative humidity); and hot, humid (37°C, 60% relative humidity). The exposure period included a 12 min exercise on a cycle ergometer. We found no significant change in spirometry, airways resistance, or diffusing capacity for either group of subjects at rest alone over the 6 hr period of exposure for any exposure condition. However, there were changes in spirometry and airways resistance as a result of the 12 min period of exercise. The subjects with asthma had significant decreases in forced expiratory volume in 1 sec (FEV1) (20–21%) and increases in specific airways resistance when exercising in conditions of cold and dry, cold and humid, and hot and dry. The normal subjects had an average increase in FEV1 of approximately 6% when exercising in the hot and humid conditions. We found significant correlations for the changes in FEV1 with the water content of the exposure conditions for both groups of subjects. We also found that the work performance (expressed as the external work performed divided by the oxygen consumed) was decreased for the subjects in both groups at the conditions of the higher temperature (37°C) compared with the lower temperature (10°C). These results confirm that controlling for the conditions of temperature and humidity is essential in chamber studies, field studies, or epidemiologic evaluations determining the adverse effect of an air pollutant.