The psychiatric history and presenting clinical characteristics of 276 depressed primary care patients with and without a lifetime comorbid anxiety disorder were studied in a randomized control trial of treatments for major depression. Our findings indicate that distinctive patterns of depressive symptoms and severity, functional impairment, comorbidity of other DSM-III-R Axis I and Axis II disorders, and treatment participation are associated with lifetime histories of panic and generalized anxiety disorder. The most consistent differences are evident between patients with major depression alone and those with major depression and a lifetime panic disorder. The latter presented with greater depressive severity, greater impairment in physical and psychosocial functioning, and were more likely to have a history of alcohol dependence, somatization disorder, and avoidant personality disorder. Discriminant function analysis indicated that 66% of depressed patients with lifetime panic disorder could be correctly distinguished from those without such comorbidity on the basis of the severity of somatic and affective symptoms but not cognitive symptoms of depression. Further, depressed patients with lifetime panic disorder were more likely to prematurely terminate both pharmacotherapy and psychotherapy during each treatment's acute phase. Implications for the diagnosis and treatment of major depression with comorbid anxiety disorder in primary care patients are discussed.