The dependence of the rates of oxidative metabolism of drugs and toxic chemicals on tissue oxygen concentration and hence on bodyweight is established. Consequences of this for species differences in the rates of deactivation of drugs and activation of toxic chemicals are considered, especially for the veterinary prescription of drugs and for the use of experimental animal models in the safety evaluation of drugs and chemicals. The high rate of oxidative activation of toxic chemicals in the mouse, the high level of hepatic cytochrome P-448, and the high potential for autoxidative tissue injury in this species, are considered to make it an inappropriate animal for chronic toxicity and carcinogenicity studies.