BACKGROUND: Late life depression can be successfully treated with antidepressant medications or psychotherapy, but few depressed older adults receive effective treatment. RESEARCH DESIGN: A randomized controlled trial of a disease management program for late life depression. SUBJECTS: Approximately 1,750 older adults with major depression or dysthymia are recruited from seven national study sites. INTERVENTION: Half of the subjects are randomly assigned to a collaborative care program where a depression clinical specialist supervised by a psychiatrist and a primary care expert supports the patient’s regular primary care provider to treat depression. Intervention services are provided for 12 months using antidepressant medications and Problem Solving Treatment in Primary Care according to a stepped care protocol that varies intervention intensity according to clinical needs. The other half of the subjects are assigned to care as usual. EVALUATION: Subjects are independently assessed at baseline, 3 months, 6 months, 12 months, 18 months, and 24 months. The evaluation assesses the incremental cost-effectiveness of the intervention compared with care as usual. Specific outcomes examined include care for depression, depressive symptoms, health-related quality of life, satisfaction with depression care, health care costs, patient time costs, market and nonmarket productivity, and household income. CONCLUSIONS: The study blends methods from health services and clinical research in an effort to protect internal validity while maximizing the generalizability of results to diverse health care systems. We hope that this study will show the cost-effectiveness of a new model of care for late life depression that can be applied in a range of primary care settings.