To investigate possible associations of nodular regenerative hyperplasia (NRH) with antitumor chemotherapy, we reviewed 72 partial hepatic resections (55 with metastatic tumor, 12 hepatocellular carcinomas, and five benign neoplasms). Thirty autopsy livers from adults without malignancies served as controls. Studies included hematoxylin and eosin, reticulin, and trichrome stains and immunostaining for proliferating cell nuclear antigen (PCNA). Five of 72 livers (7%) had NRH. All five patients had received chemotherapy, one by intrahepatic artery infusion. Four had received chemotherapy 2 months or less before undergoing partial hepatectomy. These five cases represented 15% of the 33 patients who received chemotherapy. No NRH was seen in autopsy control livers. In contrast to NRH, multiple hyperplastic foci were seen in 28 of 72 livers (39%). This finding did not correlate with chemotherapy. Two of 30 control livers (7%) showed similar mild regenerative changes. In only one case of NRH was PCNA staining increased over controls. A band of PCNA-positive hepatocytes was seen adjacent to the tumor in 21 cases, suggesting that the presence of tumor may cause a local increase in PCNA expression. Mitoses in hepatocytes and assessment of the thickness of liver cell plates were more sensitive indicators of regeneration than PCNA. Vascular changes, such as sinusoidal fibrosis (11 of 72 cases), thickened hepatic arterioles (13 of 72 cases), and mild thickening of central veins (10 of 72 cases), did not correlate with NRH, hyperplastic foci, or chemotherapy. No cases of hepatoportal sclerosis were identified.