The analyses reported in this paper were based on the survey responses of the 15,259 participants aged 12-17 years (8,005 in 1991 and 7,254 in 1992). To minimize the impact of non-medical drug use among adolescents on family structure, respondents were excluded if they reported initiating non-medical drug use before their current age minus 1 year. With this exclusion, there remained 13,648 individuals at risk for initiating non-medical drug use in this interval (7,053 in 1991 and 6,595 in 1992). Non- medical drug use refers to non-medical use of cocaine/crack, marijuana, heroin, hallucinogens, inhalants, stimulants, tranquilizers, sedatives, and/or analgesics. Multiple logistic regression models in the conditional form were used to assess the association between family structure and initiating non-medical drug use, holding constant other suspected confounding variables. To hold constant unmeasured socio-environmental confounding factors, the study used an epidemiological strategy that involved post-stratification of adolescents into neighborhood risk sets. The findings show that adolescents living in families without both parents were more likely to initiative non-medical drug use, but these associations varied by sex. These results help measure the impact of divorce/separation/death and/or remarriage of parents on adolescents and identify subgroups at higher risk for initiating non-medical drug use. 2 tables and 58 references