Hepatic necrosis, rarely occurring after administration of modern halogenated general anesthetics, has been ascribed to free radical-induced lipoperoxidation. As evaluation of hepatic chemiluminescence has been shown to provide a noninvasive assay for oxidative radical reactions, we have made continuous in vivo measurements of hepatic light output in the phenobarbital-induced halothane anesthetized rat and compared them with observations made during chloroform anesthesia. Chloroform produced a far more rapid and more profound increase in chemiluminescence, a phenomenon probably related to depletion of hepatic glutathione. These findings are consistent with significant differences in hepatic pathology associated with the two agents.