1 The effects of K(+), NaCN and the ionophores monensin, nonactin and carbonyl-cyanide-p-trifluoro-methoxyphenylhydrazone (FCCP) on the contents of [(3)H]-5-hydroxytryptamine ([(3)H]-5-HT), [(3)H]-dopamine and [(3)H]-noradrenaline ([(3)H]-NA) in guinea-pig synaptosomes preloaded with these amines were measured.2 In the presence of Ca(2+), K(+) markedly reduced the amine content of the synaptosomes, indicating an acceleration of spontaneous amine release. In the absence of Ca(2+), K(+) had much less effect.3 Monensin, nonactin and FCCP caused a release of all the three labelled amines. This release was considerably faster and more marked than that induced by K(+) and showed no dependence on Ca(2+). The ionophores did not release lactate-dehydrogenase from synaptosomes.4 NaCN, a blocker of oxidative energy production, did not enhance the spontaneous release of [(3)H]-5-HT nor did it influence the monensin-induced release of [(3)H]-5-HT.5 It is concluded that (a) the intragranular storage of 5-HT, dopamine and NA is dependent on the maintenance of a pH-gradient across the granular membrane as well as on the granular membrane potential; (b) the ionophores cause a non-exocytotic release of granular amines, and (c) blood platelets are partial models for aminergic brain neurones as far as intragranular amine storage is concerned.