This family study explores the controversial relationship between unipolar major depression and alcoholism. Thirty-nine families of patients with non-psychotic unipolar depression and alcoholism, 160 families of patients with non-psychotic unipolar depression without alcoholism, and 64 families of patients with alcoholism without psychotic or major affective disorders were compared with 109 families of unscreened probands recruited in the general population. Both disorders were familial. They were transmitted independently in families; a sharing of substantial genetic or of other familial components between the two disorders was unlikely to occur in the sample under study, particularly among male subjects. Comorbidity between the two disorders was more common than expected by chance, but excess comorbidity was preferentially mediated by non-familial factors. Reasons for discrepancies among the conclusions of different family studies on these issues are discussed.