D-Galactosamine is a known hepatotoxin which induces liver cell necrosis via depletion of UTP and other uridine nucleotides. Our previous work indicated that nodular hepatocytes have higher levels of total uridine nucleotides compared to normal liver, and in the present study we investigate the effect of galactosamine treatment on hepatocyte nodules and surrounding liver. Hepatic nodules were generated in male Wistar rats according to the Solt and Farber protocol. Six months after initiation animals received a single injection of D-galactosamine (500 mg/kg i.p.) and were then killed 1, 2, 4 or 7 days later. Histological analysis of liver revealed the presence of extensive liver cell necrosis in normal tissue 1 and 2 days after galactosamine treatment. However, very little or no necrosis was detectable inside hepatic nodules at any time point, indicating that these focal areas are resistant to the cytotoxic effect of galactosamine. This type of resistance could be the expression of a new component in the resistant phenotype of hepatic nodules.