The role of Pavlovian conditioning in the development of tolerance to the hypothermic effect of ethanol and of cross-tolerance to hydralazine was investigated. In the first study, two groups of rats were treated on alternate days with ethanol (2 or 4 g/kg, respectively, IP) in a novel and distinctive environment (DR). On the non-alcohol days, they received saline in the home room (HR). A control group received saline in both environments. Tolerance to the hypothermic effect of ethanol in the DR was demonstrable in both the 2 and 4 g/kg treatment groups. Tolerance in the HR, however, was observed only in the 4 g/kg treated group. Cross-tolerance to the hypothermic effect of hydralazine was observed for both ethanol-treated groups in the DR but not in the HR. In the second study, ethanol treatment was carried out by daily intubation with 6 g/kg ethanol in the home cage. Tolerance to ethanol-induced hypothermia was demonstrated either in the home cage or in a novel environment. This treatment, however, failed to confer cross-tolerance to the hypothermic effect of hydralazine. These findings suggest that conditioning plays a predominant role in the tolerance produced by low but not by high treatment dosage. The data also suggest that conditioning might be a separate component in tolerance development, which is of special importance in tolerance to behavioral effects in the whole animal rather than to cellular or molecular effects.