An in-school youth survey for a major state anti-tobacco media campaign was conducted with 1,831 students (Grades 6-12) from 70 randomly selected classrooms throughout the state. Tobacco users accounted for nearly 25% of the sample. Pretest questionnaires assessed demographic variables, tobacco use, and various other risk factors. Several predictors of adolescents' susceptibility to tobacco use, including prior experimentation with tobacco, school performance, parental smoking status, parents' level of education, parental communication, parental relationship satisfaction, best friend's smoking status, prevalence of smokers in social environment, self-perceived potential to smoke related to peer pressure, and psychological reactance, were examined using discriminant analysis and logistic regression to identify the factors most useful in classifying adolescents as either high-risk or low-risk for smoking uptake. Results corroborate findings in the prevention literature indicating that age, prior experimentation, and having friends who smoke are among the principal predictors of smoking risk. New evidence is presented indicating that psychological reactance also should be considered as an important predictor of adolescent smoking initiation. The utility of producing antismoking messages informed by an awareness of the key risk factors-particularly psychological reactance-is discussed both in terms of the targeting and design of anti-tobacco campaigns.