The authors have refined a model of cirrhosis in the rat and used it to determine whether the administration of halothane anesthesia adversely affects preexisting liver disease. Male Wistar rats were placed on phenobarbital water and were assigned randomly to two groups. Group 1 rats were exposed by inhalation to carbon tetrachloride (CCL4at weekly intervals for 12 exposures while Group 2 rats received only air. All treatment including phenobarbital then was withdrawn for 4 weeks. Rats then were bled for SGOT and SGPT determinations and 24 h later were exposed to 1.8% halothane in oxygen for 3 h (HAL); the remaining rats from each group were exposed to 100% oxygen for 3 h (O2). Twenty-four hours later, rats were killed and blood was obtained for SGOT and SGPT by cardiac puncture. Light microscopic histologic examination was performed blind on liver sections for cirrhosis and scored for superimposed acute focal necrosis. The weekly sublethal CCl4exposure resulted in histologically demonstrable cirrhosis in all surviving Group 1 animals. The mean (±SD) SGOT (128±32IU/±1) and SGPT (86±24IU/1) values for the Group 1 rats were significantly greater (P< 0.01) than those for Group 2 rats (98±18 IU/1 and 57±12 IU/1, respectively). Cirrhotic animals showed neither deterioration in liver function nor acute liver cell necrosis after Hal compared with O2. However, Group 2 rats showed a modest but significant increase in SGOT (P < 0.05) after HAL, while this change was not noted after O2. Thus, 1.8% halothane anesthesia in oxygen did not result in superimposition of acute liver cell injury in already cirrhotic rats.