Results show at age 16 negative affect was a positive statistical predictor of age 18 substance use, controlling for prior substance use. Although the estimated effect was not large in magnitude, this finding is consistent with certain prior research which suggests that some individuals may turn to substance use to escape from or cope with their symptoms of negative affect. However, other studies have not supported the self-medication hypothesis among teens. There were several estimated effects of the covariates on the primary variables in this study: early substance use at age 11 was associated with a higher level of substance use from age 16 to 18. Increased substance involvement during the transition from middle to late adolescence appeared to be driven more by proximal factors, such as negative affect in middle adolescence, than by distal indicators of early substance use. Although male gender was associated with peer deviance in expected ways, it was negatively related to substance use in middle adolescence, indicating that boys were less likely than girls to use substances at age 16; and impulsivity was a significant positive predictor of negative affect at age 16. Data were collected from Project Family, a panel study of rural sixth graders and their families, some of whom participated in brief universal substance use preventive interventions. Tables, figures, and references