Double-blind, placebo-controlled trials have documented the efficacy of some monoamine oxidase (MAO) inhibitors in treating certain depressed patients. This preliminary report of a 6-week, double-blind, placebo-controlled study of the MAO inhibitor isocarboxazid (Marplan) examines the time course of platelet MAO inhibition and treatment response, and describes symptoms that distinguish markedly improved from slightly improved responders. Thirty male outpatients, ages 28-64, randomly divided into placebo (n = 15) and active medication (n = 15) groups, were followed weekly. Medication was started at 20 mg daily and increased to achieve 90% platelet MAO inhibition. Data were analyzed for 24 patients who completed at least 3 weeks of the study. A clinician's global change rating at the study's conclusion showed that 12 of 13 patients (92%) in the active medication group improved, while 3 of 11 (27%) patients in the placebo group improved. Significant symptomatic improvement occurred in the active treatment group by week 3. Trends suggest that anxiety improved first (week 2), followed by depression (week 3), and finally cognitive outlook (week 6). Only minimal difficulties were observed with orthostatic hypotension, hypertensive crises, or other side effects. At baseline, the only significant difference between the markedly improved and slightly improved groups was greater psychomotor retardation in the markedly improved group. Trends suggest that the markedly improved group showed less depression, anxiety, sleep disturbance, and weight loss, fewer gastrointestinal complaints, and more helplessness and worthlessness.