This study addresses the issue of whether the increased rates of substance-related problems for family members of cocaine abusers are specific for each substance. The present analysis examined the prevalence of problems due to alcohol or drug use separately for mothers, fathers, sisters, and brothers using the Family History Assessment Module. The probands were 343 out-of-treatment subjects with DSM-III-R cocaine disorders who did or did not have additional alcohol and opiate disorders. After accounting for age, race, gender, and antisocial personality, family history of alcohol-related problems had an odds ratio of 1.6 (p < .05) if a participant was alcoholic in addition to abusing cocaine. Specifically, a significantly greater proportion of participants' sisters (p < .001) and brothers (p < .05) had alcohol-related problems if the participant had a history of alcoholism. Among probands who reported opiate abuse or dependence, 38% had relatives with drug-related problems, while participants without opiate abuse or dependence had less than 31 % of relatives with drug-related problems (p < .05). However, this association with opiate abuse or dependence family history of drug-related problems was non-significant after controlling for participants' age, race, gender, treatment status, and antisocial personality diagnosis (odds ratio = 1.4, 95% C.I. = 0.8-2.4). Associations between participants' alcoholism and first-degree relatives' drug-related problems (and vice versa) showed that participants' history of opiate addiction did improve prediction of first-degree relatives' alcohol-related problems, except for participants' brothers. Additional family risks for alcoholism were seen among siblings of drug abusers who also reported abuse of or dependence on alcohol even after controlling for relatives' ages. Furthermore, parental prevalence of alcohol-related problems were greater when participants had opiate addiction in addition to cocaine addiction. This seems to indicate that opiate addiction in addition to cocaine addiction has particularly strong inheritance patterns. In contrast, parental prevalence of drug-related problems mas not greater when participants had alcohol addiction in addition to cocaine addiction. Thus, the cross-substance parent-child familial risk is limited to the dually diagnosed illicit drug.