The effects of the opiate antagonist naloxone (0.4 mg.kg-1, i.v.) on carotid chemoreceptor and ventilatory responses to graded steady-state levels of hypoxia and hypercapnia were investigated in two groups of cats: chronically normoxic and chronically hypoxic. The cats of the latter group were exposed to PIO2 of about 70 mm Hg at sea level for 3-4 weeks and showed an attenuated response to hypoxia. All cats were tested under alpha-chloralose anesthesia. Naloxone treatment did not increase appreciably carotid chemoreceptor activity or its responses to hypoxia and hypercapnia in either cat group. Naloxone caused a small ventilatory stimulation in the chronically hypoxic cats, so that the attenuated response to hypoxia was not relieved. By contrast, the chemoreflex ventilatory response to hypoxia was stimulated by naloxone in the chronically normoxic cats. The findings that the depressed ventilatory chemoreflexes in the chronically hypoxic cat were not ameliorated by the opiate antagonist indicate that an increased elaboration of endogenous opiates does not underlie ventilatory adaptation to chronic hypoxia.