The livers of 345 autopsy cases of chronic liver disease were examined for macroregenerative nodule (MRN), a large nodular lesion more than 10 mm in diameter. A total of 86 lesions of MRN was found in 49 cases (14.2%): 32 were from 191 cases of hepatocellular carcinoma (HCC), 16 were from 148 cases of cirrhosis only, and one was from six cases of chronic hepatitis. The incidence (19.6%) and the size (12.1 mm) of MRN in macronodular type of cirrhosis were significantly higher and larger than those in other types of cirrhosis. Also, the average size of MRN lesions of cases with HCC (12 mm) was significantly larger than that of cases with cirrhosis only (10.5 mm). The incidence of liver cell dysplasia (LCD) in cases of MRN (67.3%) was significantly higher than that in cases without MRN (40.9%). The MRN lesions were divided into Type I and Type 11, the latter having proliferative foci distinguishable from the surrounding tissue. Three of them contained atypical cells regarded as cancer. Type I1 lesions were larger in size, and cases with multiple MRN lesions were seen more frequently in cases of HCC. The average age of the patients with Type 11 lesion was 5 years older than those with Type I lesions. These findings suggest that MRN should not be ignored in the morphogenesis of HCC.