The combination of a tricyclic and a monoamine oxidase inhibitor (MAOI) has been reported effective in the treatment of depression but is avoided in this country due to concern over adverse reactions. A review of the case reports on which this concern with morbidity is based reveals no convincing evidence that the antidepressant combination taken in therapeutic doses was responsible for the illness reported. An informal review of 350 outpatients, a record examination of 50 inpatients, and a drug trial with 10 current patients has shown no drug-related morbidity. We conclude that the present evidence does not indicate the combined drug regimen unsafe. A suggestion is made for controlled clinical trials of MAOI-tricyclic antidepressant therapy to evaluate better its clinical effectiveness.