The effect of adenosine on the vasodilator response of the rat mesenteric arterial bed to electrical field stimulation of perivascular sensory-motor nerves was examined. Adenosine (0.3-10 microM) produced a concentration-dependent attenuation of the vasodilator response to electrical stimulation of sensory-motor nerves, which is mediated by the sensory neuropeptide calcitonin gene-related peptide (CGRP). The adenosine receptor antagonist, 8-phenyltheophylline (1 microM) competitively antagonized the inhibitory effect of adenosine. Adenosine did not affect the vasodilator response to exogenous CGRP, thus indicating that the inhibitory action of adenosine on the vasodilator response to perivascular sensory-motor nerve stimulation was prejunctional.