• We measured platelet tritiated imipramine binding and serotonin uptake in 51 depressed patients and 43 normal controls. Although there were no significant differences in platelet 3H-imipramine binding or serotonin uptake when the total group of depressed patients was compared with controls, depressed women (n = 32) had a significantly lower maximal density of 3H-imipramine binding sites (βmax) than control women (n = 25). Moreover, among the total group of depressed patients, there were significant negative correlations between the βmax values and plasma cortisol levels at 4 PM (n = 41) and 11 PM (n = 41) following dexamethasone administration. These negative correlations between βmax and cortisol levels were strongest among melancholic patients both at 4 PM before dexamethasone administration (n =14) and at 11 PM after dexamethasone administration (n =15). These data suggest that the reported decrease in βmax found among depressed patients may be related to and is perhaps secondary to the hypercortisolemia of depression.