Eighteen depressed outpatients were treated far 6 wk with a mean daily dose of 121 mg of nortriptyline. The mean plasma level was 138 ng/ml during treatment. Therapeutic response was monitored by the Zung Self-Rating Depression Scale and the Hamilton Depression Scale administered by two psychiatrists blind to the tricyclic used, dose, and plasma levels. Eight patients recovered (Hamilton ≤ 6) by the fourth week and 12 by the sixth week. During the steady-state (wk 4 to 6) there was a positive correlation between the weekly Hamilton scores and the weekly nortriptyline levels (p < 0.01). The 9 patients with mean plasma levels between 50 and 139 ng/ml had a better therapeutic response after 6 wk measured by percent recovered (p < 0.005), Zung score (p < 0.05), and Hamilton score (p < 0.025) than the 9 patients with mean plasma levels between 140 and 260 ng/ml.