OBJECTIVE Outpatient clinical trials with an opioid antagonist, naltrexone, found that this agent reduces relapse drinking in abstinent alcoholics. It is unknown which aspects of intoxication may be affected by naltrexone. The authors investigated the effects of naltrexone on several subjective and objective measures of ethanol intoxication. METHODS In a double-blind crossover study, 19 nonalcoholic drinkers received a regimen of naltrexone, 50 mg p.o., or placebo on two different occasions, each time followed by a standard, intoxicating dose of ethanol. Subjective and objective measures of intoxication including mood, physical sensations, performance changes, and ethanol pharmacokinetics were determined. As a control for naltrexone effects, 12 additional subjects received naltrexone or placebo followed by a non-intoxicating, "placebo" dose of ethanol. RESULTS Naltrexone augmented certain sedative and discriminant effects of ethanol and reduced positive reinforcing effects without affecting psychomotor performance or ethanol pharmacokinetics. Naltrexone had minimal effects in subjects receiving placebo ethanol. CONCLUSIONS The data are compatible with the clinical findings and suggest that the reduction in ethanol consumption by alcoholics following naltrexone administration may occur because of greater subjective intoxication, greater aversive effects, or less positive reinforcement from ethanol.