3H-Lysergic acid diethylamide (3H-LSD) binding, a putative measure of 5-HT2 receptor binding, was studied in the blood platelets of 29 depressed patients and 24 normal controls. The Bmax (maximum number of 3H-LSD binding sites) in the blood platelets of depressed patients was significantly greater than that of normal volunteers. This increase in Bmax was due to an increase in female depressed patients only. Bmax was significantly lower in female compared to male normal controls but there was no difference between male and female depressed patients. There was also no difference in Kd (an inverse measure of affinity of 3H-LSD binding to its sites) between normal controls and depressed patients. The correlations between Bmax of 3H-LSD binding and the Bmax of the 3H-imipramine binding site or the Vmax of 5-HT uptake sites were not significant. The role of serotonergic processes in the psychobiology of depression is discussed.