Endogenous opiates are found in large concentrations in the brainstem of vertebrate animals, suggesting that they play a possible role in the central control of breathing. To examine this possible role in human ventilatory control we evaluated the effect of nalozone, a specific opiate antagonist, on the ventilatory and mouth occlusion pressure (P0.1) responses to hypercapnia and hypoxia in 6 normal men 22 to 48 yr of age. In a random double-blind crossover study, each subject received both an intravenous infusion of 50 mg of naloxone and a placebo infusion of normal saline. Ventilatory responses were measured before and 5 min after each infusion. Ventilatory responses to hypercapnia and hypoxia were more marked after both the saline and naloxone infusions, but there was no significant difference in the responses between the 2 infusions. Similarly there was no significant difference in respiratory timing or mean inspiratory flow between the 2 infusions at an arterial oxygen saturation (SaO2) > 95%. We concluded that endogenous opiates have no major influence on the chemical control of breathing in normal humans.