Subtotal colectomy and ileorectal anastomosis in familial adenomatous polyposis patients can induce temporary regression of adenomas in the rectum. The mechanism for this phenomenon is unclear. We evaluated the effect of colectomy on rectal mucosal proliferation, in relation to changes in bile acid metabolism. Four familial adenomatous polyposis patients were studied before and 3-6 months after surgery, and eight others 7-22 years postoperatively. Within 6 months after surgery, the size of the proliferative zone of the colonic crypts was found to be reduced (P less than 0.05). The proliferative activity of total colonic crypts was not affected within this period. More than 7 years postoperatively, increased cell proliferation of total crypts (P less than 0.02), as well as mid (P less than 0.05) and basal (P less than 0.05) crypt compartments, were observed compared to shortly after colectomy. In duodenal bile, deoxycholic acid was absent shortly after operation, whereas several years after operation only a small fraction (2%) was present. Fecal secondary bile acid excretion diminished after colectomy and did not change several years postoperatively. In postoperative stools only, small proportions of ursocholic and ursodeoxycholic acids (about 5% each) were consistently found. As subtotal colectomy causes a temporary decrease in the length of the proliferative zone of rectal crypts toward a normal pattern, this may explain regression of rectal polyps. This temporary effect may be mediated, at least in part, by decreased amounts of cytotoxic secondary bile acids in the rectal lumen.