The purpose of this study was to elucidate the etiological pathways towards substance use and risky sexual behavior in female adolescent substance abusers. The study had three aims: (1) to determine the relations between behavioral dysregulation, negative affectivity, and childhood victimization with substance use and risky sexual behavior, (2) to determine whether these relations are mediated by internalizing symptomatology, antisocial behavior, and affiliating with an adult boyfriend; and (3) to determine whether age of menarche moderates the relation between the mediating variables and substance use and risky sexual behavior. Multiple behavioral, psychiatric interview, and self-report measures were used to index behavioral dysregulation, negative affectivity, childhood victimization, internalizing symptomatology, antisocial behavior, affiliation with adult boyfriends, substance use, and risky sexual behavior in 125 substance abusing female adolescents and 78 controls between the ages of 14-18 years. Structural equation modeling was used to determine the etiological pathways. Results indicated that behavioral dysregulation, negative affectivity, and childhood victimization were related to substance use and risky sexual behavior. Age of menarche was significantly correlated with affiliation with an older boyfriend and risky sexual behavior. Antisocial behavior mediated the associations between behavioral dysregulation, negative affectivity and childhood victimization with substance use and risky sexual behavior. Affiliation with an adult boyfriend was directly associated with substance use involvement and accounted for the relationship between chronological age and risky sexual behavior. Finally, late menarche enhanced the association between internalizing symptomatology and substance use involvement. The results highlight the importance of behavioral dysregulation, negative affectivity, and childhood victimization in predicting substance use and risky sexual behavior, as well as the finding that antisocial behavior and affiliation with an adult boyfriend may be etiologically important in predicting these outcomes. Therefore, from a prevention and treatment standpoint, behavioral and affective dysregulation, childhood victimization as well as antisocial behavior may serve as clinical 'gateways' for altering the developmental trajectory toward substance use and risky sexual behavior in high risk and substance abusing youth. For example, reducing dysregulation through behavior modification procedures that have been developed for conduct disordered children would appear to be a heuristic avenue of investigation emanating from the results obtained in this study.