Students in 22 urban schools completed self-report questionnaires with measures of drug use (smoking, drinking and marijuana use) at three annual assessments. For participating students (n=2,354), analyses of variance were conducted to test for ethnic group (Asian, Black, Hispanic, White) and gender differences in polydrug use. Ethnic differences were found for polydrug use measures at each assessment point. Asian and Black adolescents generally reported less polydrug use than White and Hispanic youth. When gender differences were evident, boys engaged in more use than girls. The relatively high rates of polydrug use indicate that prevention intervention programs that target multiple substances may be more efficient in reducing overall risk than prevention programs that focus on a single substance. Table, references