Sesquiterpene lactone extract from the leaves of Vernonia amygdalina was tested for antihepatotoxic activity. Adult male rats were selected for the study. One group of rats was treated with toxic doses of carbon tetrachloride (CCl4) the second group was pretreated with known concentration of terpenoid extract from leaves of V. amygdalina. One hour prior to receiving toxic doses of CCl4, Kolaviron, a biflavonoid extract of the seeds of Garcina kola was used as a positive control. Serum enzymes, alanine amino transferase (ALT), ornithine carbamoyl transferase (OCT) that are known to be very sensitive to cytotoxic hepatic injury, and aspertate amino transferase (AST) that is particularly sensitive to carbon tetrachloride poisoning, were measured as indices of hepatotoxicity. The results obtained showed that there were reduction in the activities of serum ALT, AST and OCT from 20.57 +/- 5.59, 10.46 +/- 6.71 and 184.8 +/- 10.45 in animals treated with toxic doses of CCl4 to 3.40 +/- 0.10, 3.95 +/- 0.15 and 1293 +/- 12.10 in animal pretreated with terpenoid extract before CCl4 intoxication, representing 83.5%, 62.3%, and 30% decrease respectively. These decreases were statistically significant (P < 0.001, P < 0.05, P < 0.001 respectively). From these results, it is concluded that sesquiterpene lactone extract from the leaves of V. amygdalina like kolaviron, a biflavonoid extract from the seeds of G. kola has antihepatotoxic activity in CCl4-induced hepatic damage in rats.