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Street-involved youth experience high rates of alcohol and other drug use, which put them at risk for other health-related problems including substance dependence, infectious diseases, drug overdose and victimization. There is limited research on gender differences in poly-substance use among street-involved youth. In this study of 150 street youth in Toronto, Canada, we explore the effects of gender, health and social factors on alcohol and other drug use. Multivariate regression analyses were used to create models predicting the number of substances (alcohol and illicit drugs) used in the last 30 days before interview. * The Youth Pathways Project [YPP]: Other members of the team include Co-Investigators/Collaborators, Edward Adlaf, Jennifer Butters, Deborah Goodman, Andrew Hathaway, Bruce Leslie, Paul Links, Lori Ross, Christine Wekerle; Community Partners, Toronto Children’s Aid Society, Catholic Children’s Aid Society, SHOUT Clinic; Research Staff, Katharine King (Project Coordinator), Tara Fidler, Tyler Frederick, Eman Leung. The mean number of substances used by the female and male street youth was 2.1 and 2.5, respectively, with up to seven used in total.