A pilot population-based study of a microsatellite polymorphism at the DRD5 locus in adult European-Americans showed its association with childhood symptom counts for oppositional defiant disorder (ODD) in males and females and adult antisocial personality disorder (ASPD) in females. No association with childhood conduct disorder symptom count was observed. ODD mediated the genotype-ASPD relationship in females. Neither ODD nor ASPD significantly mediated the relationship between the genotype and the liability to substance dependence (SD). The data suggest involvement of the DRD5 locus in the variation and sexual dimorphism of SD liability and antisociality and in the developmental continuity of antisociality.