Commonly used experimental mammals, such as the rat and mouse, exhibit hypothermia and hypometabolism when exposed acutely to many drugs and other chemical substances. This toxic-induced hypothermic/hypometabolic state may be an inherently protective response that can reduce the lethality of a toxic insult. However, as body mass increases, the ability to lower body temperature in response to toxic insult is diminished. Hence, the presence of a protective hypometabolic/hypothermic response in small laboratory mammals and apparent lack thereof in larger species, such as humans, may represent an additional physiological dissimilarity which may underestimate the risk assessment of acute toxicological data.