Acamprosate (calcium-acetyl homotaurinate) is a relatively new compound developed for the treatment of alcoholism and has been shown to be effective in attenuating relapse in human alcoholics. In the current study, the effects of this drug were further examined using an animal model of oral ethanol self-administration in a limited access paradigm. Male Wistar rats were trained to respond for ethanol (10% w/v) or water in a two-lever free-choice operant condition. Acute administration of acamprosate (400 mg/kg) reduced ethanol consumption and increased responding for water. Chronic administration of lower daily doses of acamprosate (100 and 200 mg/kg) blocked the increased ethanol consumption typically observed in rats after an imposed abstinence period. This effect of acamprosate was selective for ethanol, as responding for water was unaffected at any dose tested. These results with rats suggest a model by which to explore the mechanisms for anti-relapse effects of acamprosate.