To clarify the functions of hepatic metallothioneins (MTs) after the administration of endotoxin (lipopolysaccharide : LPS), we investigated the expression on MT genes in the bacterial endoxin-treated rat liver by Norhern blot hybridization and in situ hybridization methol with riboprobes synthesized from mouse cDNA of MT-Ⅱ chronologically. Northern blot analysis revealed a rapid increase in the amount of MT gene transcripts in the liver 3 hours after the administration of LPS, with a maximum at 6 to 12 hours followed by a gradual decrease. In the in situ hybridization method, MT genes are expressed in the liver lobule for 3 hours after the adiminstration of LPS, and hepatocellular damage was observed at 6 hours after the LPS administration initially and expanded most extensively at 18 hours. During this peripd, MT genes are expressed in intact tissue intensely and specifically. At 24 hours after the administration, transcripts of the MT gene were detected in intact hepatocytes around the shrinking necrotic area. These findings suggest that MTs protect the liver cells by scavenging the free radicals, which probably cause liver cell damage due to LPS administration, and that MTs provide the zinc ions necessary for stabilizing the cell membrane and to heal the liver cell damge.