The effects of adenosine, ATP and adenosine beta, gamma-methylene-5'-triphosphate (APPCP) were compared in the saphenous vein of the dog. Adenosine and ATP in concentrations which did not affect the response to exogenous noradrenaline, depressed that to nerve stimulation; this effect was antagonized by theophylline. APPCP increased tension in unstimulated veins and in those made to contract with noradrenaline and nerve stimulation. The results suggest that the inhibitory effect of ATP on adrenergic neurotransmission is due to its rapid breakdown to adenosine, which acts on prejunctional P1 purinoceptors.