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OBJECTIVE: The identification of predictors of major depression in the transition to adulthood has direct application to prevention and intervention efforts designed to forestall depression in this high-risk period. The current study identified childhood and adolescent familial and behavioral-emotional factors predicting depression during this critical developmental stage. METHOD: The 354 participants were part of a single-age cohort from a predominately Caucasian working-class community whose psychosocial development has been traced prospectively since age 5. In these analyses, data collected during childhood and adolescence were related to diagnoses of major depression at ages 18–26. RESULTS: During the transition to adulthood, 82 participants (23.2%) experienced major depression. Bivariate indicators of later depression included a family history of depression or substance use disorders, family composition, and childhood family environments perceived as violent and lacking cohesiveness. Also significant were self- and mother-reported internalizing behaviors, as well as self-rated anxiety and depressive symptoms. Multivariable analyses showed family violence, family composition, internalizing problems during adolescence, and low family cohesion to be the most salient factors. CONCLUSIONS: These results highlight familial and behavioral-emotional predictors of depression that can serve as foci for identifying youth in need of intervention.