The platelet monoamine oxidase (MAO) activity of 557 male Ss, ages 21–26 years, was assessed with substance use and abuse, family history of alcoholism, and personality traits. Low platelet MAO activity was associated with (a) undercontrolled behavioral style as evidenced by high scores on measures of antisociality, (b) increased use of cigarettes, and (c) increased rates of illicit drug use and adverse consequences of drug use. Low MAO activity was not related to either alcohol use or abuse. In an experimental study, 17 Ss with MAO activity in the lowest decile and 38 Ss with MAO activity in the highest 2 deciles were administered either a .625 g/kg dose of alcohol or a placebo and exposed to an anxiety-provoking stressor. Low-MAO-activity Ss appeared to show stronger stress response dampening on heart rate than high-MAO-activity Ss. No other differences in response to alcohol were found, and MAO activity was not related to general reactivity to the stressor.