Given the changing racial/ethnic composition of the United States, the impact of culture on adolescent health risk behaviors is an emerging and important issue. The purpose of the present study was to examine acculturation and ethnic identity and its impact on substance use, depression, and self-esteem in a sample of middle school students. Further, this study examined peer influence as a potential mediating factor in the relationship between acculturation and drug and alcohol use. Results showed that acculturation and ethnic identity were unrelated to depression and self-esteem, and the integration acculturation strategy did not predict substance use. The Sobel Test revealed that peer influence did not mediate the relationship between acculturation and ethnic identity but it was significantly related to lifetime substance use. Moreover, the rate of lifetime substance use for this sample was double the national substance use rates for adolescents. These findings provide information for school counseling personnel in identifying risk and protective factors for substance use in early adolescents. Additionally, these findings provide support for including multicultural responsive services in substance use prevention programming in schools. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]