It has been hypothesized that the formation of oxygen-derived free radicals may play an important part in ischemically induced tissue injury. Using a canine ischemic liver model, we have assessed the role of two oxygen-free radical scavengers, catalase (CAT) and superoxide dismutase (SOD), used alone and in combination, on the recovery of ischemic livers. Liver ischemia was induced in adult mongrel dogs by cross-clamping of the portal vein and hepatic artery for 40 min. Hepatectomy was then performed, and livers were tested in an isolated perfusion model with 500 ml of an albumin-mannitol solution at 37 degrees C for 3 hr. Liver function tests were performed hourly during the perfusion period. Biopsies and 99m-Tc-HIDA scans were also done at the end of perfusion. Livers in group 1 (n = 6) served as controls and were not pretreated prior to ischemic injury. Livers in group 2 (n = 6), group 3 (n = 6), and group 4 (n = 6) were pretreated, respectively, with CAT (5000 U/kg), SOD (5000 U/kg), and SOD and CAT in combination (5000 U/kg) each. The results indicated that the oxygen-derived free radical scavengers, CAT and SOD, were able to provide partial protection against the free radicals accumulated during ischemic damage. These studies offer some potential avenues for the protection of livers prior to and after transplantation.