Disagreement remains as how to interpret elevated scores on measures of self-reported distress. This study compared elevated scores on the Center for Epidemiologic Studies-Depression Scale (CES-D) in 2 samples to mood disturbance as assessed in an interview. In a primary medical care sample, most distressed patients did not have a mood disturbance, and distress without mood disturbance was associated with little impairment. Primary care patients with elevated scores on the CES-D were less distressed and less likely to have mood disturbance, major depression, or impairment than distressed psychiatric patients. Few patients with mood disturbance in either sample failed to meet criteria for major depression. Implications are discussed for research on depression using self-report measures, for generalizations across clinical and nonclinical populations, and for screening for preventive interventions.