Recently research into the mechanism of action of antidepressant drugs has focused on mechanisms that could account for the delayed onset of therapeutic action. Chronic treatment with antidepressants elicits a delayed reduction in numbers of beta-adrenergic receptor binding sites as well as norepinephrine sensitive adenylate cyclase. Besides catecholamines, serotonin mechanisms have been thought to play a major role in the actions of antidepressants. We have characterized two discrete serotonin receptors using ligand binding techniques. S 1-receptors are labelled selectively by 3 H-serotonin and S 2-receptors bind 3 H-spiroperidol, while 3 H-LSD has equal affinities for S 1 and S 2 receptors. Relative potencies of drugs in competing for S 1-receptors show some correlations with effects on adenylate cyclase. Taken together with the regulation of S 1-receptors by guanine nucleotides, a characteristic of adenylate cyclase linked receptors, we suggested, that S 1-receptors may have some association with adenylate cyclase.