Recent research suggests that dopaminergic/noradrenergic system dysfunction may be associated with substance abuse and/or antisocial behavior. In order to determine whether male youth of fathers with these disorders would manifest differences in these systems when compared with youth of nonsubstance-abusing or nonantisocial fathers, levels of homovanillic acid (HVA), the metabolite of dopamine (DA) and dopamine-β-hydroxylase (DBH), the enzyme facilitating the conversion of dopamine to norepinephrine, were studied in offspring blood samples. The subjects were 65 male youth aged 6–15 years admitted to a residential center because of behavioral disorders. Parental substance abuse and antisocial behavior were assessed through interviews, rating scales, and/or chart review. HVA and DBH were determined from blood samples obtained after admission. The findings indicated that youth of substance-abusing fathers had significantly greater levels of HVA than youth of nonsubstance-abusing fathers. Younger (<12.0 years) boys of antisocial fathers had significantly lower DBH activity than comparably aged youth of nonantisocial fathers. The results suggest that common generational links in substance abuse and antisocial behavior in males may be associated with detectable biological parameters in susceptible youth.