Peptic ulcer disease (PUD) remains a well-known sequela of renal transplantation, and, when complications occur, morbidity and mortality can be significant. For this reason, all patients at our center undergo a pretransplant upper gastrointestinal series (UGI). Patients with evidence of active ulcer disease on UGI and/or a history of PUD undergo upper gastrointestinal endoscopy and do not undergo transplantation until healing is demonstrated. Following transplantation, antiulcer prophylaxis is utilized for 6 weeks (in patients without pretransplant PUD) or 3 months (in patients with pretransplant PUD). To help define the incidence and significance of PUD in the cyclosporine era, as well as the value of pretransplant screening and posttransplant ulcer prophylaxis, a retrospective chart analysis of 254 patients who underwent renal or renal/ pancreas allograft transplanted between January 1984 and December 1989 was accomplished. Twenty-six patients (10%) presented with symptomatic PUD at a mean of 7.8 months posttransplant. The incidence of PUD was 10% in patients with a negative pretransplant history and UGI, 15% in patients with a positive pretransplant history and negative UGI and endoscopy, and 0% in patients with a positive pretransplant history and UGI. Age, sex, primary disease, donor source, and number of rejection episodes were not significantly different in recipients with or without PUD. At the time of presentation, 23 patients (88%) had completed their antiulcer prophylaxis. Four patients (15%) died secondary to ulcer disease including two of three (66%) following surgical treatment and two of 23 (9%) during medical treatment. Posttransplant PUD continues to result in significant morbidity and mortality in the cyclosporine era. Pretransplant screening, including UGI and endoscopy, is not a reliable predictor of posttransplant, symptomatic PUD. Based on this study, it is concluded that all patients should receive longer periods of antiulcer prophylaxis, independent of previously defined pre- and posttransplant risk factors.