Abstract The hepatotoxicty of d-galactosamine was evaluated using the isolated perfused rat liver. In controls, ATP- and UDPglucose-levels decreased by about 20% during 12 hr of perfusions; UTP + UDP as well as the energy charge remained constant. d-Galactosamine reduced the contents of UDPglucose and UTP + UDP to 10 to 20% of normal within 30 min, whereas the sum of all acid-soluble uracil nucleotides increased linearly for the first 8 hr. The leakage of intracellular enzymes into the perfusion medium was small and almost linear in controls; in livers treated with d-galactosamine, however, a sharp increase occurred after 6 hr. Addition of uridine 3 hr after d-galactosamine prevented cell damage as judged by enzyme release. E. coli endotoxin, either alone or after preincubation with rat serum, did not enhance enzyme leakage. Lightmicroscopically, liver cell plates were partially dissociated and necroses of groups of liver cells were found in galactosamine-treated livers. In electron microscopy, degenerative changes of hepatocytes were seen after galactosamine perfusion.