The effect of endotoxin administration on zinc metabolism was studied in rats. In the endotoxin-treated rats, serum zinc concentration was significantly reduced as compared to saline-treated rats (control group). On the other hand, hepatic zinc concentration was significantly increased after endotoxin administration as compared to the control group. However, the zinc concentrations of the liver cell components showed slightly dissimilarity. In the mitochondria and cytsol, the concentration increased significantly after endotoxin administration as compared to the control group, whereas no change was observed in the microsomes. Furthermore, we have examined whether the increase of the zinc level in the cytosol of the liver is associated with zinc-binding protein metallothioneins (MTs) or not. MTs also increased significantly after endotoxin administration. Furthermore hepatic MTs were analyzed for MT isoforms. In the endotoxin-treated MT-II was the major Iso-MT. Judging from these results and some other published reports, the role of zinc metabolism in endotoxemia is proposed to be as follows. In endotoxemia the serum zinc concentration is reduced and as a result the production of superoxide by polymorphonuclear leukocytes is increased as zinc has an inhibitory effect on it. This free radical helps the host against the organism. On the other hand zinc accumulation in the liver following endotoxin administration increases the activity of the zinc binding-enzyme and also stabilizes the plasma membrane. MTs induced by endotoxin protect the host from the harmful effects of the free radical in the host by its scavenging action.