The relationship between DNA synthesis activities of hepatocytes in biopsied specimens and liver volume was studied in various stages of primary biliary cirrhosis using an in vitro bromodeoxyuridine (a thymidine analogue)-anti-bromodeoxyuridine reaction and computed tomography. The mean bromodeoxyuridine (+/- SE) labeling index for 10 patients in an early histological stage (stage I, 4, and stage II, 6, 3.4% +/- 0.4%) of primary biliary cirrhosis was 17 times that for 6 control subjects (0.2% +/- 0.1%, P less than 0.001), and was significantly higher than that for 19 female patients with chronic aggressive hepatitis (0.9% +/- 0.2%, P less than 0.001), 14 compensated cirrhotic patients of viral origin (all female, 1.1% +/- 0.3%, P less than 0.01), and 5 patients with stage III primary biliary cirrhosis (0.5% +/- 0.1%, P less than 0.001). The mean (+/- SE) liver volume in the early stage of primary biliary cirrhosis (1225 +/- 40 cm3) was about 1.5 times that in control subjects (835 +/- 42 cm3, P less than 0.001). These results suggest that liver volume has already become large in the early stage of primary biliary cirrhosis perhaps because of markedly increased DNA synthesis in hepatocytes.