The effect of theophylline (a P1-purinoceptor blocker) on the tritium release evoked by high KCl (50 mM) and l-epinephrine (3 microM) was evaluated using [3H]adenosine-prelabeled pulmonary artery of the rabbit. It has previously been shown that KCl elicits purine release from adrenergic nerve terminals whereas epinephrine releases it from postsynaptic sites in this artery. The KCl-induced [3H]purine efflux was significantly enhanced by theophylline (10-100 microM), whereas the efflux induced by epinephrine (3 microM) was not enhanced but reduced by this drug at 100 microM. In contrast to theophylline, 1 to 3 microM adenosine or ATP significantly suppressed the KCl-induced purine efflux. This depolarization-induced efflux was not augmented by 10 microM papaverine or 3 microM phentolamine. Uptake of [3H]adenosine into the pulmonary arterial segment was strongly inhibited by 10 microM dipyridamole or papaverine, but not by the same concentration of theophylline. These findings suggest that the presynaptic autoinhibition mechanism may be involved in the purine release from vascular adrenergic nerves.