When a small amount of Gram-negative lipopolysaccharide was intravenously injected into mice which had been injected with heat-killed Propionibacterium acnes 7 days before, massive hepatic cell necrosis was induced and most of the mice died 24 hr later. However, when prostaglandin E1 was administered with lipopolysaccharide, remarkable improvements in the survival rate and in the histological changes of the liver were observed. In order to find out how prostaglandin E1 suppressed the induction of massive hepatic cell necrosis in this experimental model, we studied the effects of prostaglandin E1 on the activation of liver adherent cells, from which the cytotoxic factor is released, and on the protection of hepatocytes from the cytotoxic factor. As a result, prostaglandin E1 not only inhibited the activation of liver adherent cells and suppressed the release of the cytotoxic factor, but it also directly affected the hepatocytes and protected them from the cytotoxic factor.