We hypothesized that there is an association between the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism with the variability in exercise heat tolerance in humans. Fifty-eight Caucasian men were exposed to a 2-h exercise heat-tolerance test. We analyzed the association between their heat-tolerance levels with the ACE DD (n = 25) and I+ (n = 33) genotypes and with various anthropometrical parameters and aerobic fitness. It was found that the relative changes in body core temperature, heat storage, and heart rate during the 120-min exposure to exercise heat stress was consistently lower in the I+ genotype group compared with the DD genotype group (0.8 +/- 0.2 vs. 1 +/- 0.1 degrees C, P < 0.05; 17.7 +/- 1.8 vs. 19.8 +/- 1.3 W/M(2), P < 0.05; and 33 +/- 7 vs. 44 +/- 5 beats/min, respectively, P = 0.06). No significant association was found between heat strain response and the anthropometrical measurements or aerobic fitness in the various genotype groups. We suggest that the ACE I+ polymorphism may be considered as a possible candidate marker for increased heat tolerance.