Influence of parental alcohol/substance abuse on methadone maintenance therapy (MMT) outcome was examined in 164 DSM-III-R opioid dependent adults with no other current DSM Axis I disorder. Family history positive patients had more DSM-III-R opioid dependence symptoms and were more likely to be classified as severely dependent. However, when placed on identical daily doses of methadone (50 mg), they had lower rates of illicit opioid use but higher rates of cocaine use than family history negative patients. Both effects remained significant after adjusting for gender and race. These results suggest that common genetic factors may underlie both susceptibility to heroin dependence and response to therapeutic methadone treatment.