Seventeen patients with cirrhosis and histologically defined, ultrasonically detected, large regenerative nodules of the liver were followed without treatment for more than 1 yr (range = 13 to 51 mo). During the follow-up period, none of the nodules were demonstrated sonographically to have enlarged. Computed tomography and/or hepatic angiography were also performed in 14 patients, but there was no evidence of malignant transformation in these lesions. None of the 17 patients showed acute elevation of serum alpha-fetoprotein levels. Furthermore, four nodules became undetectable by these imaging procedures. Follow-up biopsy performed in seven patients revealed no significant histological changes from the first biopsy sample. However, HCCs developed apart from these large regenerative nodules in four patients. These HCCs suddenly appeared and did not seem to have been derived from preexisting large regenerative nodules. From these observations, it was not possible to regard a large regenerative nodule having no cytological atypia as a high-potential premalignant lesion. Their precancerous potentiality needs to be compared with that of ordinary pseudolobules.