The carotid body is influenced by many neurotransmitter receptors. A novel receptor specific for imidazolines has been implicated in cardiorespiratory regulation in the brain. To test for both I1-imidazoline and alpha2-adrenergic receptors, which also recognize imidazolines, specific [125I]p-iodoclonidine binding to carotid body membranes was characterized. The specific alpha2-agents epinephrine (100 microM) or SK&F 86466 (10 microM) inhibited only a portion of specific [125I]p-iodoclonidine binding in both cat and rabbit carotid bodies, indicating the presence of I1-imidazoline as well as alpha2-adrenergic sites. The distribution of [125I]p-iodoclonidine binding sites was visualized autoradiographically. The cat carotid body was intensely labeled by [125I]p-iodoclonidine, with both I1-imidazoline and alpha2-adrenergic sites expressed. The relevance of I1-imidazoline receptors in modulation of chemosensory discharge was determined in seven cats after alpha2-adrenergic blockade. Clonidine (100 microg/kg) facilitated chemosensory activity particularly under hypoxia. We conclude that I1-imidazoline receptors are expressed within the carotid body and may potentiate chemosensory discharge, in contrast to the inhibitory action of alpha2-adrenergic receptors.