Mexican American adolescents report high rates of internalizing symptomatology and alcohol use. However, very little research has explored to what extent internalizing distress may contribute to alcohol use among this population. The current study utilized longitudinal data from a community sample of Mexican American adolescents (n=626, 51% female) to test a series of hypotheses about the role of internalizing distress on alcohol use and misuse. Specifically, this study used a bifactor modeling approach to investigate (1) whether different forms of internalizing distress are composed of common and unique components; (2) whether and to what extent such components confer risk for alcohol use; and (3) whether youth cultural orientation plays a role in these associations. Confirmatory factor analyses revealed that a bifactor model with a general factor and three specific factors (depressed mood, general worry, social anxiety) provided good fit to the data. The general distress factor was significantly associated with past month alcohol use but not binge drinking. However, these effects were conditional based on level of acculturation. Differential relations were found between the specific factors of internalizing distress and alcohol use. Depressed mood predicted past month alcohol use among girls; social anxiety negatively predicted past three month binge drinking among boys. Overall, results highlight the multidimensional nature of internalizing distress and suggest that both common and unique components of internalizing distress may be relevant to the etiology of alcohol use among Mexican-American adolescents. Findings underscore the importance of considering cultural orientation as a moderating factor when investigating substance use among Hispanic youth. Implications for future research examining the etiological relevance of the internalizing pathway to alcohol use among Hispanic adolescents are discussed.