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The present study examines the relationship of familial and personality risk factors for alcoholism to individual differences in sensitivity to the positively and negatively reinforcing properties of alcohol. Sixteen sons of male alcoholics with multigenerational family histories of alcoholism (MFH) and 11 men who self-report heightened sensitivity to anxiety (HAS) were compared with 13 age-matched family history negative, low anxiety sensitive men (FH-LAS) on sober and alcohol-intoxicated response patterns. We were interested in the effects of alcohol on specific psychophysiological indices of “stimulus reactivity,” anxiety, and incentive reward. Alcohol significantly dampened heart rate reactivity to aversive stimulation for the MFH and HAS men equally, yet did not for the FH-LAS group. HAS men evidenced idiosyncrasies with respect to alcohol-induced changes in electrodermal reactivity to avenive stimulation (an index of anxiety/fear-dampening), and MFH men demonstrated elevated alcohol-intoxicated resting heart rates (an index of psychostimulation) relative to the FH-LAS men. The results are interpreted as reflecting a sensitivity to the “stimulus reactivity-dampening” effects of alcohol in both high-risk groups, yet population-specific sensitivities to the fear-dampening and psychostimulant properties of alcohol in the HAS and MFH groups, respectively.