BACKGROUND Depression, a clinically heterogeneous syndrome, may also be etiologically heterogeneous. Using a prospective, epidemiologic, and genetically informative sample of adult female twins, we identify and validate a typology of depressive syndromes. METHODS Latent class analysis was applied to 14 disaggregated DSM-III-R symptoms for major depression reported over the last year by members of 1029 female-female twin pairs. RESULTS Seven classes were identified, of which 3 represented clinically significant depressive syndromes: (1) mild typical depression, (2) atypical depression, and (3) severe typical depression. Severe typical depression was characterized by comorbid anxiety and panic, long episodes, impairment, and help seeking. Atypical depression was similar in severity to mild typical depression, but was characterized by increased eating, hypersomnia, frequent, relatively short episodes, and a proclivity to obesity. Individuals with recurrent episodes tended to have the same syndrome on each occasion. The members of twin pairs concordant for depression had the same depressive syndrome more often than expected by chance and this resemblance was greater in monozygotic than in dizygotic pairs. CONCLUSIONS In an epidemiologic sample of female twins, depression is not etiologically homogeneous, but is instead made up of several syndromes that are at least partially distinct from a clinical, longitudinal, and familial/genetic perspective.