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Objective: To estimate the occurrence and school-level clustering of drug involvement among school-attending adolescent youths in each of seven countries in Latin America, drawing upon evidence from the PACARDO research project, a multinational collaborative epidemiological research study., Methods: During 1999-2000, anonymous self-administered questionnaires on drug involvement and related behaviors were administered to a cross-sectional, nationally representative sample that included a total of 12,797 students in the following seven countries: Costa Rica (n = 1,702), the Dominican Republic (n = 2,023), El Salvador (n = 1,628), Guatemala (n = 2,530), Honduras (n = 1,752), Nicaragua (n = , 419), and Panama (n = 1,743). (The PACARDO name concatenates PA for Panamá, CA for Centroamérica, and RDO for República Dominicana). Estimates for exposure opportunity and actual use of alcohol, tobacco, inhalants, marijuana, cocaine (crack/coca paste), amphetamines and methamphetamines, tranquilizers, ecstasy, and heroin were assessed via responses about questions on age of first chance to try each drug, and first use. Logistic regression models accounting for the complex survey design were used to estimate the associations of interest., Results: Cumulative occurrence estimates for alcohol, tobacco, inhalants, marijuana, and illegal drug use for the overall sample were, respectively: 52%, 29%, 5%, 4%, and 5%. In comparison to females, males were more likely to use alcohol, tobacco, inhalants, marijuana, and illegal drugs; the odds ratio estimates were 1.3, 2.1, 1.6, 4.1, and 3.2, respectively. School-level clustering was noted in all countries for alcohol and tobacco use; it was also noted in Costa Rica, El Salvador, Guatemala, and Panama for illegal drug use., Conclusions: This report sheds new light on adolescent drug experiences in Panama, the five Spanish-heritage countries of Central America, and the Dominican Republic, and presents the first estimates of school-level clustering of youthful drug involvement in these seven countries. Placed in relation to school survey findings from North America and Europe, these estimates indicate lower levels of drug involvement in these seven countries of the Americas. For example, in the United States of America 70% of surveyed youths had tried alcohol and 59% had smoked tobacco. By comparison, in these seven countries, only 51% have tried alcohol and only 29% have smoked tobacco. Future research will help to clarify explanations for the observed variations across different countries of the world. In the meantime, strengthening of school-based and other prevention efforts in the seven-country PACARDO area may help these countries slow the spread of youthful drug involvement, reduce school-level clustering, and avoid the periodic epidemics of illegal drug use that have been experienced in North America.