The effect of buspirone, a drug with mainly 5-HT1A-agonist activity, on voluntary ethanol intake was tested in a rat model of alcoholism. In this model the treatment consists of an injection of ethanol (2.0 g/kg) or saline once a week, preceded by a 24 h choice between water and ethanol (10% w/v). This weekly injection of ethanol reduces voluntary ethanol intake in male rats. Maximal inhibition is seen after 5-6 weeks. At this maximal inhibition buspirone or saline was injected prior to the voluntary 24 h intake of ethanol in both the ethanol- and saline-injected groups. The tested doses were 5 mg/kg (week 5) and 20 mg/kg (week 6). There was no reduction in ethanol intake in the buspirone-injected groups when compared with their corresponding controls. A second experiment with buspirone was performed during the evaluation period following treatment with ethanol. This treatment consisted of a choice between water and ethanol (10%, w/v) for 1 day each week, followed by an injection of ethanol 2.0 g/kg) and lasted for 52 weeks. During the evaluation period the rats had a continuous choice between ethanol and water for 37 weeks and no injections were given. In this situation, with a longer exposure to ethanol, a dose of 20 mg/kg of buspirone in week 90 reduced ethanol intake by approximately 40%, when compared with controls. The effect of this buspirone dose lasted at least a week. This indicates that the long-term exposure to ethanol in the second experiment induces changes that affect the serotonergic transmission, and that this changed neural system is involved in the regulation of voluntary ethanol intake.