This study determined the influence of exercise intensity, protective clothing level, and climate on physiological tolerance to uncompensable heat stress. It also compared the relationship between core temperature and the incidence of exhaustion from heat strain for persons wearing protective clothing to previously published data of unclothed persons during uncompensable heat stress. Seven heat-acclimated men attempted 180-min treadmill walks at metabolic rates of approximately 425 and 600 W while wearing full (clo = 1.5) or partial (clo = 1.3) protective clothing in both a desert (43 degrees C dry bulb, 20% relative humidity, wind 2.2 m/s) and tropical (35 degrees C dry bulb, 50% relative humidity, wind 2.2 m/s) climate. During these trials, the evaporative cooling required to maintain thermal balance exceeded the maximal evaporative capacity of the environment and core temperature continued to rise until exhaustion from heat strain occurred. Our findings concerning exhaustion from heat strain are 1) full encapsulation in protective clothing reduces physiological tolerance as core temperature at exhaustion was lower (P < 0.05) in fully than in partially clothed persons, 2) partial encapsulation results in physiological tolerance similar to that reported for unclothed persons, 3) raising metabolic rate from 400 to 600 W does not alter physiological tolerance when subjects are fully clothed, and 4) physiological tolerance is similar when subjects are wearing protective clothing in desert and tropical climates having the same wet bulb globe thermometer. These findings can improve occupational safety guidelines for human heat exposure, as they provide further evidence that the incidence of exhaustion from heat strain can be predicted from core temperature.