This study was undertaken to assess possible modifications of the proliferative activity of colonic mucosa, which could be related to a suggested cancer-promoting role of cholecystectomy. The mitotic index (number of mitoses per 1000 gland cells) was evaluated in the colonic mucosa of 14 healthy subjects, 11 patients with cholelithiasis, before and 6 months after surgery, and 10 patients who had undergone cholecystectomy 2 or more years previously. The mitotic index of cholecystectomized patients was significantly higher than controls. It rose significantly within 6 months of cholecystectomy. The mitotic index of patients with cholelithiasis before surgery was similar to controls. These data suggest that cholecystectomy is followed by an enhancement in the proliferative activity of the colonic mucosa, which could play a cancer-promoting role.