Gender differences in the specificity of drug versus alcohol transmission were examined among 201 opioid addicts and their 877 first-degree relatives using direct interviews and a structured family history method based on the Schedule for Affective Disorders and Schizophrenia Research Diagnostic Criteria. A strong association of parental alcoholism with alcoholism among the proband addicts was found, suggesting some specificity for drug versus alcohol abuse. We also found that among the 477 siblings, those with alcoholism alone did not have parents with drug abuse and those parents with drug abuse did not have children with alcoholism alone. Rates of parental alcoholism were higher in alcoholic female than in alcoholic male probands, suggesting greater female "loading" was needed in order to become alcoholic. This increased loading in women was also found among the siblings, but alcoholic parents appeared to transmit a nonspecific tendency for either drug or alcohol abuse to their female children. Thus, it may take a greater "dose" of parental transmission for a woman to become a substance abuser, and transmission of alcoholism may be specific in men, but not in women.