This study examines neighborhood influences on alcohol, cigarette and marijuana use among a predominantly Latino middle school sample. Drawing on theories of immigrant adaptation and segmented assimilation, we test whether neighborhood immigrant, ethnic, and socioeconomic composition, violent crime, residential instability, and family structure have differential effects on substance use among youth from different ethnic and acculturation backgrounds. Data are drawn from self-reports from 3,721 7 th grade students attending 35 Phoenix, Arizona middle schools. Analysis was restricted to the two largest ethnic groups, Latino students of Mexican heritage and non-Hispanic Whites. After adjusting for individual-level characteristics and school-level random effects, only one neighborhood effect was found for the sample overall, an undesirable impact of neighborhood residential instability on recent cigarette use. Sub-group analyses by individual ethnicity and acculturation showed more patterned neighborhood effects. Living in neighborhoods with high proportions of recent immigrants was protective against alcohol, cigarette, and marijuana use for Latino students at different acculturation levels, while living in predominantly Mexican heritage neighborhoods (mostly non-immigrants) was a risk factor for alcohol and marijuana use for less acculturated Latinos. There were scattered effects of neighborhood poverty and crime, which predicted more cigarette and alcohol use, respectively, but only among more acculturated Latinos. Inconsistent effects confined to bilingual and more acculturated Latinos were found for the neighborhood's proportion of single mother families and its residential instability. No neighborhood effects emerged for non-Hispanic White students. Results suggested that disadvantaged neighborhoods increase substance use among some ethnic minority youth, but immigrant enclaves appear to provide countervailing protections.Keywords neighborhood effects; substance use; adolescents; Mexican Americans; acculturation For nearly a century the neighborhood social context has been conceptualized and investigated empirically as an important influence on the behavior of individuals. Numerous studies have tested competing theories about neighborhood effects on substance abuse among adolescents (Duncan, Duncan and Strycker 2002 1996; Elliott, et. al., 1996). Some studies have delved into differential neighborhood impacts on African Americans and European Americans (e.g., Crowder and South, 2003; Finch, Kolody and Vega, 1999). However, research is relatively sparse on the impact of neighborhoods on Latinos specifically, and how neighborhood effects operate in cities where Latinos are the largest cultural minority group (e.g., Finch, et al., 2000; Sastry and Pebley, 2003;Zatz and Portillos 2000). Thus, there is little understanding about how factors specific to predominantly Latino neighborhoods-particularly the influence of Mexican culture, immigrant populations and acculturation-may influence adolescent substanc...