Susceptibility to alcoholism varies with age, gender, and familial background. Youthful nonalcoholic males with multigenerational family histories of male alcoholism seem at particular risk. Previous investigations suggest that such males are characterized by abnormal psychophysiological response, while sober and alcohol-intoxicated; additional recent studies indicate that the endogenous opiate systems are involved in mediating ethanol reinforcement and modulating intake. We first compared cardiac response to alcohol administration among young (mean = 22.8 years), nonalcoholic men and women with multigenerational, unigenerational, and negative family histories of alcohol dependence and abuse. Then, we compared the ethanol-induced cardiac response of the males in these three groups to that of currently alcohol-dependent older males and age-matched nonalcoholic male controls. Finally, we examined ethanol-induced change in plasma beta-endorphin and cortisol levels among a subset of the nonalcoholic males, divided into those with high and low levels of postethanol administration heart-rate increase. Nonalcoholic males with multigenerational family histories of male alcoholism were characterized by significantly higher [t(301) = 5.70, p < 0.0001, Cohen's d = 0.73] levels of ethanol-induced heart-rate increase than nonalcoholics from all other comparison groups. The magnitude of their increase matched that of current male alcohol-dependents. Nonalcoholic males with high levels of ethanol-induced heart-rate increase also produced significantly more plasma beta-endorphin after consuming alcohol. Peak production of beta-endorphin was highly correlated (r = 0.861, p < 0.001) with magnitude of heart-rate increase. A subset of those at risk for alcoholism may be characterized by sensitivity to ethanol-induced reward, marked by heightened ethanol-induced, heart-rate increase, mediated by ethanol stimulation of endogenous opiate production. This subset might contain those who, once alcoholic, would differentially benefit from treatment with opiate antagonists.