The experiments reported here investigate the conditionability, using taste aversion conditioning, of the antagonistic effects of alpha-MSH on the thermoregulatory changes associated with injection of bacterial endotoxin lipopolysaccharide (LPS) in rats. Animals were administered LPS and then given alpha-MSH, as an unconditioned stimulus (UCS), in association with the novel taste of saccharin, the conditioned stimulus (CS). The temperature response at this time in alpha-MSH-treated rats was similar to that observed in control animals. However, 7 days later, when these animals were again injected with LPS but re-exposed to saccharin alone, there was a significant reduction in the temperature response profile compared to controls. These results demonstrate that in male rats the conditioned antipyretic effect following conditioning with alpha-MSH as the UCS is sufficiently robust to counteract the acute effects on body temperature of an LPS injection at the time of CS reexposure. This complements previous experiments demonstrating that thermoregulation may be influenced by cognitive association.