Monoamine oxidase (MAO) inhibitors are effective antidepressants whose use is limited because of unwanted side effects and the possibility of a tyramine-induced hypertensive crisis (cheese reaction). (-)-Deprenyl (the official nonproprietary name for this substance is selegiline), a selective MAO type B inhibitor, may be safer and have fewer side effects, but its antidepressant efficacy is uncertain. A double-blind placebo-controlled study was carried out in depressed outpatients who were treated with (-)-deprenyl in an MAO type B selective dose range and at a higher nonselective dose range. (-)-Deprenyl did not have a statistically significant antidepressant effect after three weeks of treatment at doses of 10 mg/d. However, after six weeks and at higher doses (averaging about 30 mg/d for the second three weeks), (-)-deprenyl was superior to placebo in antidepressant effect with a positive response rate of 50% vs 13.6% and with a 41% reduction in the Hamilton Depression Rating Scale mean score vs 10% in the placebo-treated group. No hypertensive crises were seen. The rate of occurrence of side effects with (-)-deprenyl was no greater than with placebo. It was concluded that (-)-deprenyl is an effective antidepressant in a dose range where it is distinguished by the absence of many of the side effects typical of nonselective MAO inhibitors.