Cystathionine gamma-lyase activity in the sera of rats subjected to experimental hepatotoxicity after intraperitoneal administration of carbon tetrachloride (CCl4) was measured and compared with activities of aspartate aminotransferase (GOT) and alanine aminotransferase (GPT), which have been clinically used for detecting liver damage. In the experimental subjects, serum levels of cystathionine gamma-lyase showed a similar behavior to GOT and GPT, increasing markedly with respect to the controls after administration of CCl4 and reaching a maximum at 24 hours. No such cystathionine gamma-lyase activity was detected immunochemically in the control subjects. These data suggest that measurement of serum cystathionine gamma-lyase activity could be used as a sensitive and specific marker of hepatic cytolysis.