A measurement model was analyzed to demonstrate a differential distribution and cumulative exposure to psychosocial risk and protective influences of adolescent drug use among ethnically-diverse adolescent samples. The sample included U.S.-born (US) Latino (N = 837), foreign-born (FB) Latino (N = 447), White (N = 632), and African American (N = 618) adolescent boys. Psychological Distress, Peer Drug Use, and Adolescent Drug Use were significantly positively correlated with Peer Drug Use and Adolescent Drug Use. In contrast, Family, School, law abidance, and guilt were significantly negatively correlated with Peer Drug Use and Adolescent Drug Use. Multiple group analyses indicated significant similarities and differences among US and FB Latinos, and Whites. Implications for early prevention, multi-level interventions, and suggestions for future research are discussed. (Contains 2 tables and 4 figures.)