Nodular regenerative hyperplasia (NRH) is a condition characterized by hepatocytic nodules distributed throughout the liver without perinodular fibrosis. The etiology is unknown, but it has been reported in patients with a variety of diseases, including autoimmune diseases and primary biliary cirrhosis (PBC). In this study, the liver biopsies of 64 patients with PBC were reviewed. Thirty-five biopsies in histological stages I or II belonging to 30 patients were suitable for study. NRH was found in 43% of biopsies (47% of patients). In 80% of these biopsies, nodular transformation was focal, while it was diffuse in the remaining 20%. Splenomegaly was more common in patients with NRH. Laparoscopy displayed evidence of portal hypertension in two of these patients and endoscopy showed esophageal varices in one patient. Serum levels of gamma-glutamyl transpeptidase were also higher in these patients. Lesions in small intrahepatic vessels, florid bile duct lesions, and portal granulomas were found more frequently in biopsies with NRH. We conclude that nodular hyperplastic changes are very common in early histological stages of PBC, and consequently, this disease should be considered in the etiology of NRH. These changes may contribute to early development of portal hypertension in these patients.