Hind-limb ischemia secondary to infrarenal aortic ligation in the rat was evaluated as a traumatic injury model for the study of the effects of trauma on the two major hepatic microsomal drug-oxidizing enzyme systems. Ischemic injury resulted in a significant decrease in hepatic cytochrome P-450 content and FAD-containing monooxygenase activity. Bilateral lower leg fracture was used as a dissimilar traumatic injury model in order to confirm these results and produced similar effects on these enzyme systems. Both forms of injury appeared to be of only moderate severity, and neither injury caused significant histopathological changes in the liver. Moreover, both injuries caused only mild hepatic damage as indicated by relatively modest elevations in glutamic-pyruvic transaminase levels. The observed reductions of cytochrome P-450 content with both forms of model injury were paralleled by decreases in the in vivo metabolism of antipyrine. Thus, it appears that trauma may have a significant, and possibly selective, effect on hepatic drug metabolism, suggesting that careful monitoring and/or dosage adjustment may be in order in some cases of post-traumatic drug therapy. Moreover, the ischemic injury produced by infrarenal aortic ligation in the rat appears to be a suitable small mammal injury model for the further study of the effects of trauma on the various hepatic drug-metabolizing enzyme systems.