OBJECTIVE: A previous study described the effect of a collaborative care intervention on improving adherence to antidepressant medications and depressive and functional outcomes of patients with persistent depressive symptoms 8 weeks after the primary care physician initiated treatment. This paper examined the 28-month effect of this intervention on adherence, depressive symptoms, functioning, and health care costs. DESIGN: Randomized trial of stepped collaborative care intervention versus usual care. SETTING: HMO in Seattle, Wash. PATIENTS: Patients with major depression were stratified into severe and moderate depression groups prior to randomization. INTERVENTIONS: A multifaceted intervention targeting patient, physician, and process of care, using collaborative management by a psychiatrist and a primary care physician. MEASURES AND MAIN RESUTLS: The collaborative care intervention was associated with continued improvement in depressive symptoms at 28 months in patients in the moderate-severity group (F-1,F-87 = 8.65; P = .004), but not in patients in the high-severity group (F-1,F-51 = 0.02; P = .88) Improvements in the intervention group in antidepressant adherence were found to occur for the first 6 months (chi(2) (1) = 8.23; P < .01) and second 6-month period (chi(2) (1) = 5.98; P < .05) after randomization in the high-severity group and for 6 months after randomization in the moderate-severity group(chi(2) (1) = 6.10; P < .05). There were no significant differences in total ambulatory costs between intervention and control patients over the 28-month period (F-1,F-180 = 0.77; P = .40). CONCLUSIONS: A collaborative care intervention was associated with sustained improvement in depressive outcomes without additional health care costs in approximately two thirds of primary care patients with persistent depressive symptoms.