Study findings show similar trends in drug use among students in Arizona and Spain, with “gateway” drugs being used by early adolescents, and with higher rates of drug use by boys than girls; however, the cross-national differences in marijuana/cannabis use were significant. Arizona preadolescents were over 25 times more likely to report marijuana/cannabis use than preadolescents in Spain. In addition, when ethnic differences were considered, Latinos in Arizona reported higher marijuana/cannabis use compared with non-Latino students. Drug-use patterns among Latino preadolescents, as well as the relevance of some risk factors among the diverse groups, were strongly influenced by their level of acculturation. Many prevention strategies focus on training adolescents to resist drug-use offers, with emphasis on resisting offers from peers. Given that the predictive power of refusal-confidence differs across populations, prevention programs should be adapted to relate to the contextual social and cultural dynamics that influence the behaviors of target populations. Findings showed that family bonding was a powerful predictor of tobacco and alcohol use among Spanish students. This suggests that prevention programs for this population should focus on the family. Data were obtained from independent samples of seventh-grade students recruited from urban public schools and surveyed in 1998. Respondents were 4,035 ethnically diverse Arizona students (Latinos and non-Hispanic Whites) and 2,243 Spanish White students. Comparisons that used odds ratios and chi-square tests were conducted in order to assess differences in drug-use rates between preadolescents in Arizona and Spain, taking gender into account. In addition, ethnicity differences in preadolescent drug use and psychosocial risk factors were explored using multivariate analysis (ANOVA and logistic regression). 4 tables, 2 figures, and 47 references