A 25-year-old man was hospitalized twice for melancholia. During the first hospitalization he had no response to a trial of desipramine but improved after the addition of lithium; during the second hospitalization he had no response to lithium but improved after the addition of desipramine. Concurrent administration of lithium and a tricyclic may be effective in some patients who respond to neither drug alone, but the sequence of drug administration may not be a critical factor.