The serotonin agonist, m-trifluoromethylphenylpiperazine (TFMPP), inhibited the K+-evoked release of [3H]acetylcholine ([3H]ACh) from rat hippocampal synaptosomes. The inhibitory effect of TFMPP was blocked by the non-selective 5-HT1 antagonist, methiothepin, but was not affected by ketanserin, mesulergine or spiperone. The 5-HT3 antagonist, MDL 72222, slightly reversed the inhibitory effect. The antidepressant, minaprine, did not modify the basal release of [3H]ACh but it antagonised the inhibitory effect of TFMPP on the K+-evoked release. The maximal reversal was found at 0.3 microM minaprine. These results suggest that minaprine interacts with heterologous presynaptic 5-HT1B receptors. A new approach is thus opened to the study of the mechanism of action of antidepressant drugs.