The mammalian carotid bodies receive sympathetic innervation from the superior cervical ganglion. The purposes of the present study were: (1) to investigate whether sympathetic innervation influences the carotid body response to hypoxia, and, if so, (2) to determine the involvement of adrenoceptors in these influence. Chemo-sensory activity was recorded from clearly identifiable action potentials from the carotid sinus nerve in 20 anaesthetized, paralyzed and artificially ventilated cats. Chemoreceptor responses to sustained isocapnic hypoxia (30 min, duration) were compared before and after carotid body sympathectomy (n = 8 cats). In response to low PO2, chemoreceptor discharge increased during the first 10 min, and plateaued for the rest of the hypoxic challenge. After sympathectomy, chemoreceptor response in the initial 10 min was the same; whereas, the magnitude of the response in remaining 20 min was significantly greater than controls (P < 0.01). Systemic administration of SKF-86466, an alpha 2-adrenoceptor antagonist augmented the hypoxic response by 80% (n = 6 cats). In presence of alpha 2-antagonist, sympathectomy had no further effect on the hypoxic response. Administration of alpha 2-antagonist in sympathectomized carotid bodies potentiated the hypoxic response, but the magnitude of potentiation was less than with intact sympathetic innervation (34% vs 80%; P < 0.01; n = 6 cats). From these results, it is concluded that (1) sympathetic innervation exerts an inhibitory influence on chemoreceptor response to sustained hypoxia, and (2) this inhibitory influence is mediated at least in part by alpha 2-adrenoceptors. The inhibitory effects of sympathetic innervation could be of importance in the efferent regulation of the carotid body activity during sustained hypoxia.