To determine the contribution of intraluminal factors to postresectional intestinal hyperplasia, cell proliferation in the distal intestine of male rats was studied after 50% proximal enterectomy or 50% proximal bypass and also after transposition of the duodenal papilla to the mid small bowel. Within 48 hr all three operations increased RNA and DNA content s in the ileal mucosa 16 to 50% over control values. At 48 hr and 1 week the response distal to resection exceeded that of bypass or pancreaticobiliary diversion; nucleic acid contents, DNA specific activity, villous height, crypt depth, and luminal circumference were greatest 1 week after resection. By 1 month, however, chemical and histological values after resection were equalled or surpassed by those in the other two groups. In excluded jejunum itself, mucosal atrophy lowered RNA and DNA contents to 60% of control levels 1 month postoperatively. Neither pancreaticobiliary diversion nor proximal enteric bypass produces the same rate of distal hyperplasia as proximal resection. Modest colonic hyperplasia may contribute to intestinal adaptation after proximal enterectomy. Adaptive postrescetional cell proliferation appears not to be mediated simply by intraluminal nutrition or enteric secretions; hormonal factors may also be important.