OBJECTIVE: Cognitive behavioral treatment has been used extensively in the acute phase of depression. The purpose of this study was to determine the applicability and effectiveness of this treatment modality in addressing the residual symptoms of primary major depressive illness. METHOD: The subjects were 40 patients with major depressive disorder who were successfully treated with antidepressant drugs. They were then randomly assigned to either cognitive behavioral treatment or clinical management of residual symptoms. In both subgroups, antidepressant drugs were tapered and discontinued. RESULTS: The group that received cognitive behavioral treatment had a significantly lower level of residual symptoms after drug discontinuation in comparison with the clinical management group. Cognitive behavioral treatment also resulted in a lower rate of relapse (15%) at a 2-year follow-up than did clinical management (35%), although this difference did not reach statistical significance. Most of the residual symptoms were found to have occurred also in the prodromal phase of illness. CONCLUSIONS: This preliminary study points to the potential clinical advantages of cognitive behavioral treatment targeted to the residual symptoms of depression.