This study reports major gastrointestinal complications in a group of 416 patients following kidney transplantation. Three hundred and ninety-nine patients received a cadaveric kidney while the other 17 received a living related organ. The immunosuppressive regimen changed somewhat during the course of the study but included azathioprine, prednisolone, antilymphocyte globulin, and cyclosporin. Perforations occurred in the colon (n = 6), small bowel (n = 4), duodenum (n = 2), stomach (n = 1), and esophagus (n = 1). There were five cases of acute pancreatitis, four of upper gastrointestinal and two of lower intestinal hemorrhage, two of acute appendicitis, one of acute cholecystitis, one postoperative mesenteric infarction, and two small bowel obstructions. Fifty percent of the complications occurred while patients were being given high-dose immunosuppression to manage either the early postoperative period or episodes of acute rejection. Ten percent of the complications had an iatrogenic cause. Of the 31 patients affected, 10 (30%) died as a direct result of their gastrointestinal complication. This high mortality appears to be related to the effects of the immunosuppression and the associated response to sepsis. Reduction of these complications can be achieved by improved surgical management, preventive measures, prompt diagnosis, and a reduced immunosuppressive protocol.