The objective of this study was to compare the effects of naltrexone (NTX) on the acquisition of alcohol drinking, during periadolescence and adulthood in rats using a rodent model of alcoholism. Periadolescent and adult alcohol-preferring (P) rats of both sexes were given access to water and 15% (v/v) alcohol 24-hr/day for 45 days. Alcohol access started at 1200 hr on post-natal day (PND) 30 for the periadolescent rats and approximately PND 90 for the adult rats. Subcutaneous (SC) injections of NTX (0, 5, 10, 20, and 30 mg/kg) were administered daily between 1600-1700 hr to separate groups of animals during the first 10 days of alcohol access. During the treatment period, differential effects on alcohol intake were seen between periadolescent and adult animals: (a) lower doses of NTX were more effective in the periadolescent than the adult P rats, and (b) greater tolerance to repeated dosing was displayed by adult, compared with periadolescent, rats. By the 20h day of alcohol access there were no significant differences between the NTX dose groups. Additionally, there were no sex of animal differences at the ages tested. These findings indicate that the endogenous opioid system(s) mediating alcohol intake are developmentally present in periadolescent P rats, such that NTX not only interfered with the acquisition of alcohol intake by adolescent P rats but appeared to also have a greater effect than that observed in adult P rats. Therefore, NTX may serve as an effective treatment in reducing alcohol abuse and dependence in genetically, and perhaps environmentally, at-risk youth.