Endogenous opioid activity has been associated with the regulation of mood and inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. We assessed differences in psychological symptomology and naloxone sensitivity in non-alcoholic males and females with a family history of alcoholism (FHP) and without a family history of alcoholism (FHN). This was followed by assessment of the association between naloxone sensitivity and psychological symptomology. Psychological symptomology was measured using the Revised Symptom Checklist (SCL-90-R) during enrollment. Adrenocorticotropin was measured following intravenous administration of naloxone/placebo. FHP males reported more obsessive-compulsive symptomology as well as increased sensitivity to naloxone relative to other groups. A positive association was observed between degree of obsessive-compulsive symptomology and naloxone sensitivity, and the association was strongest among FHP males. These findings suggest that the increased risk of alcoholism in FHP subjects (especially males) may be associated with altered opioid activity, which is expressed through an elevated level of obsessive compulsive symptomology.