The mechanisms of dopamine (DA) release central nerve endings have been investigated utilizing superfused rat striatal synaptosomes. Nomifensine was selected as a tool to discriminate between release mediated by the DA carrier and release occurring independently of the carrier. The following conclusions can be drawn from the results obtained: 1) Alterations of the sodium gradient across the synaptosomal membrane, induced by omission of extracellular Na+ or by ouabain, enhanced the release of 3H-DA from prelabeled synaptosomes. The release was blocked by nomifensine and therefore it was carrier-mediated. 2) The release of DA elicited by amphetamine and related phenylethylamines was nomifensine-sensitive, suggesting that the released DA existed from synaptosomes through the membrane carrier. 3) Depolarization of synaptosomes by high K+ triggered the release of both "newly taken up" and "newly synthesized" DA. 4) The calcium-dependent release of DA (induced by high K+, veratridine of by the ionophore A23187) was not affected by the carrier blocker nomifensine and may occur by an exocytic-like process. 5) The effects of apomorphine and neuroleptics on the stimulus-evoked release of DA do not support the existence of a presynaptic receptor-mediated inhibitory control of DA release identical to that described for noradrenaline.