Whereas adenosine is generally considered an inhibitory neuromodulator, there is evidence that adenosine may excite a variety of afferent fibers thereby evoking sympathetic activation. To determine whether adenosine also excites afferent fibers located in the forearm, adenosine was administered into the left branchial artery at doses without systemic effects while sympathetic nerve activity was monitored through a recording electrode placed in the right peroneal nerve in the lower limb. The i.a. adenosine produced a dose-dependent increase in forearm blood flow (647 +/- 209% above base line at a dose of 1.5 mg i.a.) and in muscle sympathetic nerve activity (97 +/- 30% above base line). No significant effect was observed on heart rate or systemic blood pressure. The effects of i.a. adenosine were not caused by spill over into the systemic circulation because these doses had no effect when given i.v. The increase in sympathetic nerve activity was not secondary to the local vasodilatory effects of adenosine because nitroprusside, given i.a. at doses that evoked the same degree of vasodilation, had no effect on muscle sympathetic nerve activity. The authors interpreted these results as indicative of activation of forearm afferent fibers by adenosine. The precise nature of these afferent fibers cannot be determined from these studies and may include sensory afferents and chemosensitive afferents involved in the exercise pressor reflex. By contrast with the known neuroinhibitory actions of adenosine in the central nervous system and in efferent nerves, these observations are in agreement with the concept that adenosine-induced activation of sympathetic afferent fibers is a widespread phenomenon.