Depressive illnesses are subdivided into endogenous and nonendogenous types in psychiatry throughout the world. We used one method of validating this nosologic subdivision: the determination of the extent to which the disorder is familial. Rates of depression were examined in 2,942 first-degree relatives of 566 individuals diagnosed as having unipolar major depressive disorder. Because no single definition of endogenous depression is universally accepted, four different methods for defining endogenous depression were compared: the Newcastle Scale, the Research Diagnostic Criteria, DSM-III, and the definition of "autonomous depression" proposed by investigators at Yale University (New Haven, Conn). In general, no matter which definition was used, the relatives of the patients with endogenous illness did not have higher rates of depressive illness than those of the nonendogenous group. The Newcastle Scale was the most sensitive in picking up familial transmission of recurrent unipolar depression. The results of this investigation suggest that longitudinal approaches should be added to cross-sectional approaches for the best definition of endogenous depression.