We examined the effects of a single 2.5-mg dose of melatonin on the thermoregulatory and circulatory responses to intermittent exercise at a room temperature of 27.2 ± 0.4°C (mean ± S.D.), a relative humidity of 55 ± 3% (mean ± S.D.), and a light intensity of 200-300 lux. In a double-blind cross-over study, six male participants ingested either melatonin or placebo at 11:45 hr. Participants then rested in a semi-supine position for 75 min and completed an intermittent running protocol for 66 min at alternating intensities of 40, 60 and 80% of maximal oxygen uptake. Rectal and mean skin temperature, heart rate, blood pressure, skin blood flow, subjective alertness and sleepiness, ratings of perceived exertion (RPE) and thermal strain were recorded. No effects of melatonin were found on these variables measured during the resting period (P > 0.10). During exercise, melatonin was found to moderate the increase in rectal temperature by approximately 0.25°C (P = 0.050) and magnify the increase in skin blood flow (P = 0.047). Postexercise systolic blood pressure was 7.8 ± 2.5 mmHg (mean ± S.D.) lower than before the exercise in the melatonin trial; a change which differed significantly to that in the placebo trial (P = 0.018). Melatonin did not influence subjective alertness and sleepiness before or after exercise and did not change the responses of mean skin temperature, RPE and thermal strain during the exercise (P > 0.10). In summary it is apparent that a 2.5-mg dose of melatonin has hypothermic, but not soporific, effects during 66 min of intermittent exercise performed under moderate heat stress. Whether such effects improve endurance athletic performance in hot conditions remains to be confirmed. Our data also suggest that postexercise systolic hypotension is more marked after ingestion of melatonin.