Despite the prevalence of chronic depression and its associated morbidity, there has been little systematic study of pharmacotherapy for this disorder. In this article, we report a preliminary analysis of the first 12-week phase of a multicenter clinical trial that will eventually include approximately 635 patients in acute, continuation, crossover, and maintenance studies of sertraline, a selective serotonin reuptake inhibitor (SSRI), and imipramine, a tricyclic antidepressant, for the treatment of chronic depression. Of the first 212 patients to enter the study, 168 completed all 12 weeks; of these, 61.3 percent were responders, including 58.9 percent of the 73 patients with chronic major depression and 63.2 percent of the 95 patients with double depression. Only 26.8 percent of the 198 patients for whom such data were available had ever had an adequate trial of an antidepressant medication, defined as 150 mg/day of imipramine or its equivalent taken for at least 4 consecutive weeks. In general, demographic and diagnostic characteristics were more similar than different for patients with chronic major and double depression. However, comorbid generalized anxiety disorder was significantly more common in patients with chronic major depression (11.2% threshold for chronic versus 4.9% threshold for double depression, p = .02). The results of this study provide preliminary evidence of the responsiveness of patients with chronic major or double depression to an SSRI or a tricyclic antidepressant.