The inhibition of 3H-noradrenaline (3H-NA) release by adenosine, and the possible involvement of purine receptors in the regulation of transmitter release in the portal vein were studied. The inhibitory effect of different concentrations of adenosine (10, 30, 100 and 300 microM) decreased with frequency of stimulation, but there was no marked concentration-dependence. Tetraethylammonium (TEA) enhanced the 3H-NA overflow induced by transmural stimulation. The adenosine-induced inhibition of 3H-NA overflow was antagonized by TEA. Transmural stimulation induced release of tritium from tissues prelabelled with either 3H-NA or 3H-adenine had a similar pattern of distribution. In contrast, when the rat portal vein was stimulated with (-) NA, the overflow of purine derivates was delayed and the maximum release was achieved 5 min later than the maximum induced by transmural stimulation. Phenoxybenzamine (PBA) increased 3H-NA overflow two-fold, but had no effect on the 3H-purine release induced by transmural stimulation. PBA reduced the 3H-purine release by exogenous (-) NA. These results indicate that in rat portal vein, the purine compounds have pre- and postjunctional origins and that the purine that modulates adrenergic neurotransmission might be of neuronal origin, possibly independent of adrenergic innervation.