['The present study examined the associations between internalizing disorders and substance use disorders using structural equation models to examine the relative contributions of common fixed confounding factors and direct causal pathways, and to determine the direction of causality.', 'Data were gathered during the course of the Christchurch Health and Development Study, a 25-year longitudinal study of a birth cohort of New Zealand children (n = 953). Measures included DSM-IV symptom criteria for major depression, anxiety disorders, alcohol abuse/dependence, nicotine dependence, and illicit drug abuse/dependence, ages 18, 21, and 25.', 'Structural equation modeling showed that for depression and substance use disorder, the best-fitting model was the one in which the associations were explained by a combination of common fixed factors and direct causal pathways from substance use to depression. A similar pattern emerged for anxiety disorders and (1) nicotine dependence, and (2) illicit drug abuse/dependence. The comorbidity of anxiety disorder and alcohol abuse/dependence was best explained by a model that included common fixed factors and a reciprocal pathway between these disorders. Decomposition of the correlations between internalizing disorders and substance use disorders showed that most of the correlation arose from direct causal pathways between disorders.'] Do structural models of the comorbidity of internalizing disorders and substance use disorders in a longitudinal birth cohort?