Sialic acid metabolism was investigated in the livers of control rats and of rats treated with a single oral dose (1.5 ml/kg body weight) of carbon tetrachloride. The main change observed during the necrotic stage of CCl4 poisoning (18 h after treatment) was a highly significant reduction in sialyltransferase activity. Slight reciprocal changes in neuraminidase activities, i.e., a small decrease in cytosolic neuraminidase and a small increase in the membrane bound enzyme were also observed. At 72 h after CCl4 treatment, during the stage of liver regeneration, the main change was a marked elevation in membrane-bound neuraminidase (two fold above control values). Moderate increases in the specific activities of CMP-N-acetylneuraminic acid synthetase and sialyltransferase were also observed. A considerable decrease in the sialic acid content of the isolated smooth endoplasmic reticulum (one half of control values) was detected at 72 h after CCl4 administration. The sialic acid content of the rough endoplasmic reticulum, on the other hand, remained at control levels.