We studied the putative role of endorphins in modulating hypoxic ventilatory responsiveness. In 12 healthy men, minute ventilation (VE)and mouth occlusion pressure (P0.1) responses to progressive isocapnic hypoxia were determined before and after the intravenous administration of the opioid antagonist naloxone (10 mg) or placebo. Plasma levels of beta-endorphin were measured before and after hypoxia. Naloxone did not affect the slopes or x-intercepts of the relationships between either VE or P0.1 and arterial O2 saturation. There was no correlation between the baseline plasma level of beta-endorphin and any measure of responsiveness to hypoxia. Plasma beta-endorphin levels were not affected by either short-term hypoxia or naloxone alone; however, when hypoxia followed naloxone administration, mean +/- SD beta-endorphin increased from 8.0 +/- 8.9 pg/ml to 20.2 +/- 16.6 pg/ml (p less than 0.005). We concluded that endogenous opioids do not have an important modulating influence on hypoxic ventilatory responsiveness in adult human volunteers.