Several lines of evidence suggest a role for dopamine in the pathophysiology of depression. In 1988, we reported a blunted response of growth hormone (GH) to apomorphine, a dopaminergic agonist, in endogenous depression. However, an antidepressant washout period is a major confounding factor in studies assessing the GH response to apomorphine. Indeed, whereas the influence of tricyclic antidepressants on the GH response to apomorphine is presently unknown, several reports have suggested that tricyclics may impair the GH response to clonidine for periods longer than 3 weeks following their discontinuation. In the present study, we hypothesized that a blunted GH response to apomorphine in depressed patients could be related to the recent administration of antidepressants. Therefore, the GH response to apomorphine (0.5 mg) was studied in 11 male DSM-III-R major depressive inpatients who had never received antidepressant therapy (group 1) compared to 11 normal controls and 11 major depressive inpatients drug free for at least 2 weeks (group 2). The three groups differed significantly in the GH peak response to apomorphine: mean (SD) 5.4 (4.0) ng/ml in group 1, 25.5 (10.7) in normal controls, and 5.5 (5.1) in group 2 (F = 15.5, df = 3, 30, p = 0.00001). While group 1 and normal controls (F = 21.8, p = 0.0002) as well as group 2 and controls (F = 5.6, p = 0.03) differed significantly, group 1 and group 2 did not (F = 0.18, p = 0.68). These results suggest that a washout period of 2 weeks could be sufficient in studies assessing the GH response to apomorphine.