Alemtuzumab (MabCampath, Campath-1H) is a potent lymphocyte-depleting monoclonal antibody increasingly used at induction in solid organ transplantation. Previously, it had been given by intravenous infusion; such administration is associated with a first-dose cytokine release syndrome characterized by fever and hypotension. Subcutaneous administration of alemtuzumab avoids this first-dose reaction while achieving a similar concentration to intravenous administration. The avoidance of infusion-associated hypotension is particularly important in pancreas transplantation where venous thrombosis is a major problem. We therefore treated 21 recipients of combined pancreas and kidney transplants with two 30-mg doses of alemtuzumab administered subcutaneously on days 0 and 1. No patient suffered a first-dose reaction. Lymphocyte depletion after subcutaneous alemtuzumab was profound and comparable to that seen in a group of renal transplant recipients who had received intravenous alemtuzumab. Subcutaneous alemtuzumab was associated with similar rates of acute rejection (14% at 1 year), patient survival (100%), and pancreas and kidney graft survival (95% and 100%, respectively) to those observed in centers using intravenous alemtuzumab in simultaneous pancreas kidney transplantation. There was no excess incidence of adverse events. We therefore recommend this route of administration to all transplant centers using alemtuzumab.