Level of acculturation has been linked to depressed mood in studies across culturally diverse immigrant groups. The purpose of this study was to determine the effects of acculturation, social alienation, personal and family stress, and demographic characteristics on depressed mood in midlife immigrant women from the former Soviet Union. Structural equation modeling showed that higher acculturation scores, measured by English language and American behavior, were indirectly related to lower scores for depressed mood. Higher acculturation levels promoted mental health indirectly by reducing social alienation and, subsequently, lowering family and personal stress, both of which had direct relationships to symptoms of depression. These findings support the ecological framework that guided our research and point to the importance of focusing on contextual factors in developing interventions for new immigrants.