Radioligand receptor binding techniques were used to characterize the effects of different structural types of antidepressant drugs on neurotransmitter receptors. The tricyclic antidepressants more or less potently inhibited the binding to rat brain preparations of several different radiolabelled ligands [3H]WB4101, [3H]QNB, [3H]-d-LSD, [3H]mepyramine). The potency of the nontricyclic antidepressants varied greatly. Mianserin, potently displaced [3H]mepyramine, [3H]d-LSD and [3H]WB4101 while it was very weak on [3H]QNB-binding. Nomifensine and the specific 5-HT uptake inhibitors zimelidine and alaproclate had very low affinity for these receptors. All the antidepressants tested were practically devoid of activity on [3H]DHA binding, [3H]spiroperidol binding, [3H]flunitrazepam binding, [3H]muscimol binding and [3H]naloxone binding. The implications of these findings for biogenic amine theories of affective disorders are discussed.