Thirty newly hospitalized patients with RDC major or minor depressive disorder were randomly assigned to open treatment according to fixed dosage steps with 1) amitriptyline alone, up to a maximum dose of 300 mg/day; 2) tranylcypromine alone, up to a maximum dose of 40 mg/day; or 3) the combination of amitriptyline, up to 150 mg/day, and tranylcypromine, up to 20 mg/day. For 28 patients this protocol continued for 4 weeks or until discharge. As measured by the Hamilton and Zung depression scales, patients in all three treatment groups improved equally. The combination treatment produced a nonsignificantly higher frequency of minor side effects, none of which required discontinuation of treatment. The results indicate the feasibility and safety of further controlled clinical research with combined treatment, although caution is advised.