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Based on samples of adolescents residing in urban areas in France and in Israel, cross-cultural comparisons of adolescent use of alcoholic beverages, cigarettes, and illicit drugs are reported. Lifetime and current prevalences of use of all substances are higher in France than in Israel. The relative ranking of the prevalence of use of the various drugs is identical in the two countries, and is similar to that found in American samples. In both countries, drug use is more prevalent among males than females, and among older than younger adolescents. There are no differences among different socioeconomic groups. Religiosity affects the rates of use of all drugs in France, and the rates of non-alcoholic substances and the amounts of alcoholic beverages consumed in Israel. Differences in the prevalence of substance use across cultures and within a culture decrease as overall prevalence of use increases.