To explore the relationship between central serotonergic (5-HT) function and history of parental aggression in aggressive and nonaggressive boys with attention-deficit hyperactivity disorder (ADHD). History of psychiatric symptoms was assessed in the biological parents of 41 boys with ADHD. The relationship between 5-HT function in aggressive and nonaggressive probands, as assessed via the prolactin response to fenfluramine (FEN) challenge, and parental history of aggression was examined. Aggressive boys with a parental history of aggressive behavior had a significantly lower prolactin response to FEN challenge than aggressive boys without a parental history of aggression. Nonaggressive boys had a prolactin response midway between those of the two aggressive subgroups, and their prolactin response did not vary as a function of parental aggression. Children subdivided on the basis of parental history of other psychiatric symptoms did not differ in their response to the FEN challenge. These data indicate an association between parent aggressive behavior and lower 5-HT function in aggressive boys with ADHD but do not indicate the extent to which this association is environmentally and/or genetically transmitted. There may be different neurochemical mechanisms in familial and nonfamilial aggressive children, which have clinical implications for pharmacological interventions.