Purpose: To assess the effects of naloxone, an opioid antagonist, on exercise capacity. Method: Thirteen men and 5 women (mean age = 30.1, range = 21-35 years) performed 25 watts/min incremental cycle ergometer tests to exhaustion on three days: 1) a familiarization trial, 2) following an intravenous bolus of 30 mg of naloxone or following a placebo. The order of the last 2 days was determined by a double-blind cross-over design. Minute ventilation (V_E), O₂ consumption (VO₂), CO₂ production (V CO₂), heart rate (HR) were monitored. Perceived exertion rating (0-10 scale) and venous blood samples for lactate (La^-) analysis were obtained each minute. Lactate threshold (LT) and ventilatory threshold (VT) were derived from lactate and gas exchange data, respectively. Blood pressure was obtained before exercise, 5 minutes after infusion, at maximum exercise, and 5 minutes postexercise. Results: There were no significant differences observed between the control and placebo trials. Comparing naloxone to placebo data or control data , however, demonstrated a decrease in: exercise time (96% of placebo, P<0.01), total cumulative work (96% of placebo, P<0.002), VO_2peak (94% of placebo, P<0.02), and HR (96% of placebo P<0.01). No differences were found in LT, VT, or blood pressure. In contrast, at the final common work load where load, HR, and V_E were the same, perceived exertion was higher (8.1± 0.5 vs 7.1 ± 0.4) following naloxone than placebo infusion (P<0.01). The threshold for effort perception amplification occurred at ~60 ± 4% of the placebo VO_2peak. Conclusion: Since subjects stopped exercise at levels below their measured maximum total cumulative work, VO_2peak, and HR following naloxone, these data indicate that peak work capacity was limited by the individual's perceived exertion--which can be attenuated by endogenous opioids--rather than by physiological limits.