The effects of creatine (Cr) supplementation on cardiovascular, metabolic, and thermoregulatory responses, and on the capacity of trained humans to perform prolonged exercise in the heat was examined. Endurance-trained males (n = 21) performed 2 constant-load exercise tests to exhaustion at 63 +/- 5 % VO(2max) in the heat (ambient temperature: 30.3 +/- 0.5 C) before and after 7 d of Cr (20 g x d (-1 ) Cr + 140 g x d (-1 ) glucose polymer) or placebo. Cr increased intracellular water and reduced thermoregulatory and cardiovascular responses (e.g., heart rate, rectal temperature, sweat rate) but did not significantly increase time to exhaustion (47.0 +/-4.7 min vs. 49.7 +/- 7.5 min, P =0.095). Time to exhaustion was increased significantly in subjects whose estimated intramuscular Cr levels were substantially increased ("responders" : 47.3 +/- 4.9 min vs. 51.7 +/- 7.4 min, P = 0.031). Cr-induced hyperhydration can result in a more efficient thermoregulatory response during prolonged exercise in the heat.