The involvement of the endogenous opioid system in the thermoregulatory response to sub-maximal exercise was investigated using naloxone as a pharmacologic probe. Volume-matched infusions containing either a placebo, 2 mg naloxone, or 10 mg naloxone were administered (in a randomized, double-blind, cross-over fashion) to nine physically active male volunteers (age 23.4 +/- 1.1 yr). Subjects performed 30 min of cycling at a fixed work rate (average 133 W or 54% of maximal oxygen uptake) chosen to elicit approximately 70% of the pre-determined maximal heart rate. Heart rate, blood pressure, ventilatory responses, and perceived exertion were unaffected by naloxone during exercise. Likewise, the rise in rectal temperature that occurred during exercise was essentially equivalent for placebo (0.69 +/- 0.04 degrees C increase from 0 to 30 min, P less than 0.001), 2 mg naloxone (0.60 +/- 0.04 degrees C increase from 0 to 30 min, P less than 0.001), and 10 mg naloxone (0.60 +/- 0.04 degrees C increase from 0 to 30 min, P less than 0.001). In agreement with the rectal temperature observations, naloxone did not modify sweating during exercise. Thus, insofar as naloxone may be used as an inferential tool to examine the physiologic significance of the endogenous opioid system, these data suggest that endogenous opioids are unlikely to play a significant role in the maintenance of thermal homeostasis during 30 min of sub-maximal exercise.