In a fixed-dose inpatient study, isocarboxazid produced a dose-related lowering of systolic blood pressure at weeks 2 and 4. Systolic blood pressure was also lowered by the drug in a placebo-controlled outpatient study. The magnitude of these reductions was considerable, reaching an average of 14.6 mm in inpatients who received a 50-mg dose, and 18.7 mm in outpatients. There was no evidence for a dose-related orthostatic effect, and greater orthostasis relative to placebo was found only at week 3 in the outpatient study. Significant bradycardia was produced by isocarboxazid in outpatients at weeks 2, 3, and 4 relative to placebo, but no dose-related effect was found among inpatients. Inpatients with a baseline systolic orthostatic drop of greater than or equal to 10 mm showed a significantly better response to isocarboxazid than did those with an orthostasis of less than 10 mm. The theoretical significance of these findings is discussed.