Differences in the amount of a monoclonal antibody required to inhibit R-propranolol metabolism by liver microsomes isolated from BNF or 3MC pretreated rats, mice, guinea pigs and rabbits is not due to the difference in the antibody binding constant to various 3MC induced P-450 in each species, but is due to differences in the relative abundance in the sensitive and insensitive forms of cytochrome P-450 in the microsomes. The comparison of the relative rates of antibody-sensitive formation of 4-hydroxypropranolol, 5-hydroxypropranolol and desisopropyl-propranolol from R-propranolol by the reconstituted-purified P-448 system differed markedly from the relative activities of the sensitive form(s) of cytochrome P-450 in liver against microsomes of BNF induced rats. This finding suggests strongly that the catalytic function expressed in the use of purified system does not necessarily mimic drug metabolism in microsomes.