Study participants were 503 boys attending public schools in Pittsburgh, PA, public schools, who were assessed at ages 13-19 years, with an average cooperation rate of 92.1 percent. Diagnostic and Statistical Manual (DSM)-oriented affective, anxiety and conduct disorder problems were measured with items from the caregiver, teacher, and youth version of the Achenbach scales. Scales were converted to t-scores using age- and gender-based national norms and combined by taking the average across informants. Alcohol and marijuana use were assessed semi-annually by a 16-item Substance Use Scale adapted from the National Youth Survey. When male adolescents experienced a 1-unit increase in their conduct problems t-score, their rate of marijuana use subsequently increased by 1.03 [95 percent confidence interval (CI) = 1.01, 1.05], and alcohol quantity increased by 1.01 (95 percent CI = 1.0002, 1.02). When adolescents experienced a one-unit increase in their average quantity of alcohol use, their anxiety problems t-score subsequently increased by 0.12 (95 percent CI = 0.05, 0.19). These associations were strongest in early and late adolescence. When adolescent boys experience an increase in conduct disorder problems, they are more likely to exhibit a subsequent escalation in substance use. As adolescent boys increase their intensity of alcohol use, they become more likely to develop subsequent anxiety problems. Developmental turning points such as early and late adolescence appear to be particularly sensitive periods for boys to develop co-morbid patterns of psychiatric problems and substance use. (Publisher abstract modified)