The proximal and distal extent of the compensatory response in the gastrointestinal tract of the young adult rat to resection of 10-80 percent of the combined ileum and jejunum was investigated. Thirty days after intestinal resection and subsequent end-to-end anastomosis, rats were injected with tritiated thymidine and sacrificed one hour later. The incorporation of label into colonic crypts or stomach glands was used as an index of the compensatory proliferative response. Although no compensatory response was observed in stomach glands, a significant compensatory proliferative response was found in descending colon after resections involving removal of greater than 60% of the combined ileum and jejunum. These observations imply that the compensatory proliferative response to resection is caused, at least in part, by a humoral mechanism. However, this does not exclude a role for luminal factors, intestinal blood flow, and paracrine effector substances as secondary modifiers of the compensation. The observations that resection of the small bowel can have significant effects distally on cell proliferation in the colon may be important to the planning of combination therapies which involve bowel resection in both animal models and in man.