Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication of solid organ transplantation. The University of Alberta Renal Transplant Program had not experienced a case of PTLD occurring in the early post-transplant period until March 1989. Since then, 4 patients have developed this complication. To identify the major risk factors for the recent appearance of PTLD, a retrospective analysis was carried out on 162 cadaveric renal transplants performed between July 1987 and December 1990. Four cases of polymorphic PTLD were seen. Two patients presented with fatal disseminated disease. Two others developed PTLD confined to the renal allograft; both are disease free at > 24 months of follow-up. Seventy-two (44.4%) of the cadaveric transplant recipients had received Minnesota antilymphocyte globulin (MALG) induction therapy during the study period. Twenty-four of these also received OKT3 for steroid-resistant rejection. Of the 4 patients with PTLD, 3 had received both MALG induction and OKT3; the remaining patient had received MALG induction only. The incidence of PTLD in the MALG/OKT3 group was 12.5%, which is significantly higher than that of patients receiving other immunosuppressive regimes (0.7%, P = 0.015). The incidence of PTLD was also significantly greater in the 13 patients at risk for primary EBV infection compared to the EBV seropositive patients (23.1 vs. 0.7%, P = 0.002). Only 2 seronegative patients received sequential MALG/OKT3; both developed PTLD. Thus, the population most at risk is that receiving potent antilymphocyte preparations in the setting of primary EBV infection. Allograft involvement with PTLD must be considered in the differential diagnosis of allograft dysfunction, as early diagnosis may permit the successful management of this complication.