1. Considerable evidence has been accumulated that orthologous rat and human P450 forms oxidize numerous chemicals in a highly similar manner, including the detoxication and activation of mutagens and carcinogens. 2. Nevertheless, certain specific substrates of rat P450s are not so well oxidized by the orthologous human forms, and vice versa. 3. Certain mutagens and carcinogens can be activated in a similar way by different (non-orthologous) forms in rat and man, confirming that studies on animals, directed ultimately to man, can be indicative but not predicative of chemical mutagenesis and carcinogenesis.