This study examined the effect of exogenously applied adenosine on the release of 3H-norepinephrine from the field-stimulated, superfused rat portal vein. Adenosine was found to inhibit the field-stimulated release of 3H-norepinephrine in a dose-dependent manner in 50- to 1,000-µM concentrations. The effect was reversed when adenosine was washed out. The inhibitory effects of adenosine were antagonized by theophylline (10–4M) which by itself showed a slight enhancement of stimulated 3H-norepinephrine release. ATP was found to inhibit 3H-norepinephrine release at the same concentration as adenosine while inosine was inactive. When adenosine was tested in the presence of the muscarinic and α-adrenergic blocking agents atropine and phenoxybenzamine along with indomethacin, a prostaglandin synthesis inhibitor, its inhibitory effect on the stimulated release of 3H-norepinephrine persisted. It is concluded that adenosine and/or ATP can modulate the nerve-stimulated induced release of norepinephrine presumably by an action on the adrenergic nerve termin