We report an open-label trial of sertraline in the treatment of major depression in 54 consecutive rheumatoid arthritis (RA) patients meeting DSM-IV criteria for major depressive disorder. We initially surveyed 628 RA outpatients with the Center for Epidemiologic Studies Depression Scale (CES-D) and invited those with depression to be evaluated further and treated. Eighty-four RA patients reporting depressive symptoms agreed to participate in person, and 56 met the criteria for major depressive disorder. Of these 56 patients, 54 agreed to medication treatment and were enrolled in the study. Patients were also randomized to one of three psychological treatment conditions, but for this study, conditions were collapsed because previous research on this sample indicated no significant between-group differences in depression after treatment. Patients were assessed with the CES-D and the Hamilton Rating Scale for Depression after the intervention, at 6-month follow-up, and at 15-month follow-up. At the last follow-up, 41 patients remained for assessment. In this study, sertraline was found to be a safe and efficacious treatment of depression complicating RA.