Inhalation of ethanol vapor (28 mg/l) for 24 hr caused a reduction of body temperature in rats. The mean peak blood ethanol concentration was 3.36 +/- 0.14 mg/ml. When ethanol (2 g/kg i.p.) was administered 48 hr after termination of ethanol inhalation, the ethanol vapor-treated animals maintained normal body temperatures despite the presence of blood ethanol concentrations (1.81 +/- 0.04 mg/ml) which caused hypothermia in control animals. The rate of clearance of ethanol from blood was found to be 0.34 +/- 0.01 mg/ml/hr in ethanol vapor-treated and control animals when ethanol was administered acutely 48 hr after the inhalation period. Animals tolerant to the hypothermic effect of ethanol demonstrated diminished sensitivity to the hypothermic effect of clonidine (50 micrograms/kg s.c.). Pretreatment of naive animals with the dopaminergic blocker, pimozide, significantly attenuated the hypothermic response to acute ethanol administration (2 g/kg i.p.) and potentiated the hypothermic response to acute clonidine administration. A dopaminergic mechanism may partially mediate the reduction in body temperature associated with acute ethanol administration.