Alpha-2 adrenergic receptors have been identified in numerous tissues containing norepinephrine. Carotid bodies are sensory organs that detect changes in partial pressure of arterial oxygen and contain substantial amounts of norepinephrine. However, neither the presence nor the functional significance of alpha 2-receptors in the carotid body is known. The purpose of the present study was two-fold: (1) to determine the alpha 2-receptor density in the carotid body and (2) to assess their participation in the chemoreceptor responses to hypoxia. Experiments were performed on 27 anesthetized, paralyzed and artificially ventilated cats. Alpha-2 receptor binding determined by [125I]p-iodoclonidine averaged 10 +/- 2 fmol/mg of protein (n = 18 carotid bodies). Intracarotid infusion of an alpha 2-agonist (guanabenz; 0.5, 1, and 5 micrograms/min for 5 min) caused a dose-dependent depression of the baseline activity and 5 micrograms/min reduced the magnitude of the chemoreceptor response to isocapnic hypoxia by 61% (n = 8). Systemic administration of an alpha 2-antagonist (SKF-86466, 0.5-2 mg/kg) prevented the effects of guanabenz on the chemoreceptor activity. Furthermore, alpha 2-antagonist (0.5-2 mg/kg, i.v.) alone significantly increased baseline discharge by 68% and potentiated the chemoreceptor response to isocapnic hypoxia by 46% (n = 10). These results demonstrate that (1) alpha 2-adrenergic receptors are present in the carotid body and (2) they exert an inhibitory influence on chemoreceptor response to hypoxia. It is suggested that norepinephrine may tune the carotid body responses to hypoxia in part by its action on alpha 2-receptors.