This study examines the association of risk and protective factors with substance use among 77 early adolescents (11-15 years old) with an HIV-infected parent who were interviewed in 2000-2001 in the South Bronx, a HIV high-prevalence area of New York City. The subjects were 49%female, 53% African American, and 30% Hispanic; mean age was 13 years old. A face-to-face interview was used to administer a battery of instruments representing community, family, peer, and resiliency factors. Forty percent reported ever using tobacco, alcohol or drugs; 71% were aware of their parent's HIV seropositivity. An age-adjusted path analytic model was constructed which showed: 1) family functioning predicted resiliency (a composite measure of psychological adjustment and personal competencies); 2)positive community factors and resiliency predicted less affiliation with deviant peers; and 3) poorer family functioning and affiliation with deviant peers predicted substance use. These results underscore the need for interventions that address social influence factors among vulnerable early adolescents with HIV-positive parents.