Platelet 3H-clonidine (alpha 2-adrenergic agonist) binding and 3H-imipramine binding were measured and the Dexamethasone Suppression Test performed in 17 normal controls and 14 unmedicated depressed patients in order to clarify the relationship among these three biological markers. Increases in the Bmax and the Kd for 3H-clonidine binding and decreases in the Bmax for 3H-imipramine binding of the platelets from depressed patients were observed when compared with controls. There was a significant positive correlation among 3H-clonidine Bmax, the basal (predexamethasone) plasma cortisol levels, and the severity of depression, as indicated by the Hamilton Depression Rating Scale. On the other hand, no significant correlation was observed in 3H-imipramine binding between the Bmax and the severity of depression or between the Bmax and the basal plasma cortisol levels. There was no statistically significant correlation between the Bmax of 3H-clonidine binding and that of 3H-imipramine binding in depression, but there was a trend toward correlation in normal controls.