Previously, we have reported that interleukin-6 (IL-6) administration reduces hepatic injury caused by carbon tetrachloride (CCl 4 ) and induces the production of antioxidant proteins, manganese superoxide dismutase and metallothionein. In the present study, we examined whether IL-6 was induced endogenously by CCl 4 administration in rats, and examined the relationship between the levels of IL-6 production and hepatic injury. Plasma samples were periodically collected after s.c. administration of 5 ml/kg of CCl 4 (50%, v/v, in corn oil). IL-6 was significantly produced at 1.5 hr after administration, peaked at 8 hr and gradually decreased thereafter. The activities of hepatic marker enzymes, alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) in plasma, gradually increased and peaked at 48 hr. As the ratio of the amount of corn oil to that of carbon tetrachloride was increased in the range of 1 : 0 to 1 : 8 (v/v), IL-6 induction was decreased, while ALT and SDH activities were augmented. When rats were treated with a pharmacological dose of dexamethasone (1 mg/kg), IL-6 production was decreased, but ALT and SDH activities were augmented. IL-6 expression immediately after CCl 4 administration is suggested to play some significant role in reducing hepatic injury. These findings should be thoroughly considered when the hepatic injury model is developed based on the s.c. administration of CCl 4 .