Differences in the benzo(a)pyrene metabolite pattern were shown by rodent liver microsomes (Sprague-Dawley rat) and embryo cells from Syrian hamsters and NIH Swiss mice. Rodent liver induced by methylcholanthrene shows marked quantitative variation between species. Additional pattern changes were found in mouse and hamster embryo secondary cultures with a reduction of the K-region metabolites and a marked increase in 9-hydroxybenzo(a)pyrene and concomitant reduction in 3-hydroxybenzo(a)pyrene. These results are indicative of a region-specific attack on the carcinogen by the cell monooxygenases which is distinct from the liver attack of microsomal enzymes on benzo(a)pyrene. Activation and detoxification of benzo(a)pyrene may be species and tissue variable, and susceptibility and resistance to malignant transformation may be predicated on induction of a fortuitous combination of intermediate metabolic steps.