Alcohol is the most frequently used psycho-active substance during adolescence. Adolescents who misuse or overindulge in alcohol are at risk for serious social and psychological consequences. Several preventive approaches can help adolescents deal with peer pressure that contributes to alcohol use experimentation and escalation. One promising approach involves teaching adolescents skills to refuse offers of alcohol and other drugs. Few studies, however, have examined how this approach works; that is, the connection between the prevention effort, refusal skills, and drinking behavior. This paper investigates the relationships among the intervention, refusal skills, and alcohol misuse in the Alcohol Misuse Prevention Study, a randomized, pre/post experimental study. Based on data from sixth through tenth graders (average N per grade = approximately 400), regression analyses indicate that refusal skills are significant mediators of the effect of the intervention on alcohol misuse.