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Animal but few human studies have demonstrated gender-influenced differences in outcome related to prenatal cocaine exposure. Pregnant participants in a prospective pregnancy study were interviewed for drug use. Exposure was considered positive if history or laboratory tests were positive. An ordinal measure of exposure was also constructed. Six years later, the child and primary caretaker were tested to assess drug use in the home since birth and teacher-assessed child behavior. Data were complete for 473 children (204 cocaine exposed). Twenty-four of the exposed children (12%) were considered to have persistent pregnancy exposure based on positive urine screen at delivery. Boys with any prenatal cocaine exposure scored significantly higher (more problem behaviors) than nonexposed boys on the hyperactivity item. In contrast, no similar cocaine effect was observed for girls. When cocaine exposure was expressed as the three-level ordinal variable, boys, but not girls, with persistent exposure had more behavior problems (0.5 to 1.0 SD higher). Even after control for important covariates, boys with persistent exposure had more problems in central processing, motor skills, handling abstract concepts, and passivity to the environment. The magnitude of the relations reported in this research were moderate to large. In summary, both gender and the level of exposure had a significant behavioral effect on school-age behavior. In these analyses, the behavior of boys, but not girls, prenatally exposed to cocaine was significantly and negatively affected, and these findings remained after control for covariates, including prenatal alcohol or other illicit drug exposures and postnatal drug use in the home.