Naltrexone has been evaluated in preclinical animal models of ethanol consumption and found to be effective in most reports. In clinical use, naltrexone has not proved to be as efficacious in preventing relapse. While naltrexone targets opioid receptors, many other neurotransmitter systems are targeted by ethanol and, to a greater or lesser extent, contribute to modulating ethanol's reinforcing effects. There has been indication that drugs active at the gamma amino butyric acid B (GABAB) receptors can affect the self-administration of many drugs with abuse potential. The experiments reported here evaluated the effect of three doses of baclofen (2.5, 5.0, or 7.5 mg/kg), a GABAB agonist, administered alone or in combination with a single dose of naltrexone (1.0 mg/kg). In Experiment 1, both naltrexone and baclofen, at the two higher doses tested, significantly reduced ethanol consumption in Wistar rats using a limited access procedure on Drug Days 1 and 2. When combined on Drug Days 3 and 4, baclofen/naltrexone was significantly more effective in reducing ethanol consumption than did either drug alone. Neither drug, alone or in combination, had an effect on water consumption. In Experiment 2, both baclofen and naltrexone again significantly reduced ethanol consumption, with no evidence that chronic administration across Drug Days 3 and 4 further reduced consumption compared with Drug Days 1 and 2. The clinical use of multiple pharmacotherapeutic agents in combination may allow for the use of lower doses of individual components, thereby reducing the negative side effects that contribute to lower compliance and higher relapse.