OBJECTIVE: Few trials of monoamine oxidase inhibitors (MAOIs) in tricyclic-resistant depression have had double-blind conditions. In the authors' previous double-blind comparison of tranylcypromine and imipramine in anergic bipolar depression, tranylcypromine was significantly more effective. This investigation was a crossover study of nonresponders in the initial study. METHOD: The subjects were 16 outpatients with anergic bipolar depression. Fourteen had not responded to 4 weeks of treatment with at least 30 mg/day of tranylcypromine or 150 mg/day of imipramine, and two patients were crossed over because of intolerable side effects from the initial drug. The crossover medication was prescribed as in the initial double-blind study. RESULTS: Twelve patients were crossed over from imipramine to tranylcypromine; nine of them responded to tranylcypromine. Highly significant improvements were documented on the Hamilton, Beck, and Pittsburgh Reversed Vegetative Symptom Scales. Four patients were switched from tranylcypromine to imipramine, but only one responded. CONCLUSIONS: The high rates of response to tranylcypromine in both the initial and crossover double-blind studies document the efficacy of MAOI treatment for anergic bipolar depression. Moreover, the results further illustrate the utility of MAOIs in tricyclic-resistant depressions.