The specific binding of the full agonist [3H] (-) adrenaline to platelet membranes was measured in 14 drug-free depressed patients with melancholia. There was an increased number of binding sites (Bmax) with the same apparent affinity (KD) for the radioligand, indicating that platelet alpha 2-adrenoceptor density in the high affinity state was increased in depressed patients. Long-term administration of clomipramine was associated with decreases in platelet alpha 2-adrenoceptor densities which correlated with the duration of treatment. The results support the hypothesis that in endogenous depression there is a dysfunction of the alpha 2-adrenoceptor and that antidepressant treatment might involve a time-dependent desensitization process of this receptor.