ATP (1 mM) inhibited, whereas 2-methylthio-ATP (30 mu M), a P-2Y-selective purinoceptor agonist, increased electrically evoked release of [H-3]noradrenaline from chick sympathetic neurons. The P-2X-selective purinoceptor agonist alpha,beta-methylene-ATP (30 mu M) had no effect. The ATP-induced inhibition of release as well as the facilitation caused by 2-methylthio-ATP was not affected by the selective adenosine (P-1) receptor antagonist 8-(p-sulfophenyl)-theophylline (8-PST; 100 mu M), but completely prevented by the non-selective P-2 antagonist suramin (300 mu M). The present data reveal a dual regulation of noradrenaline release from sympathetic neurons. Facilitation seems to be mediated by a P-2Y purinoceptor, whereas inhibition is caused by a P-2 purinoceptor which needs further subtype characterization.