Introduction. Fabry’s disease is associated with an increased incidence of thrombotic events and rejection. Spontaneous thrombosis of a functioning cadaveric renal allograft in a recipient with Fabry’s disease prompted prospective evaluation of all transplant candidates with Fabry’s disease for hypercoagulability. Materials and Methods. Transplant candidates with Fabry’s disease were tested for hypercoagulability, analyzed for HLA-type and ABO group, and comorbid conditions suggestive of hypercoagulability. Results. A unique association of Fabry’s disease with activated protein C Resistance was documented in a cohort of Caucasian male renal transplant recipients with Fabry’s disease. Four of five patients were blood group A and had no significant comorbid conditions suggestive of hypercoagulability. The resistance to activation of protein C (APCR)(1) patients shared HLA loci-B8 and Dr3, although the APCR(-) patients shared HLA loci-B27 and -B38. Conclusions. Due to the observed increase in the incidence of APCR in our Fabry’s cohort, we suggest screening all patients with Fabry’s disease for APCR. Because factor V and factor Va receptors are found on vascular endothelium and peripheral blood monocytes, APCR in the presence of Fabry’s disease may be a nonimmunological stimulus for rejection. Analysis of HLA typing in patients with Fabry’s disease may further elucidate HLA-based association of Fabry’s disease and resistance to activated protein C with the risk of thrombosis and rejection. Fabry’s disease is an X-linked recessive disorder of glycosphingolipid metabolism characterized by deficient tissue activity of a-galactosidase A. It has a reported incidence of 1:40,000 in the United States. A MEDLINE search between 1990 and 1999 documents a disturbing pattern of thrombotic events (1, 2) in patients with Fabry’s disease including retinal infarction, stroke, myocardial infarction, and deep venous thrombosis. UNOS registry data demonstrate long-term renal allograft survival has been reported but most transplant centers remain cautious when considering patients with Fabry’s disease for transplantation. Case reports of renal allograft and other solid organ transplant loss due to thrombosis are plentiful in recipients with Fabry’s disease (3, 21, 24, 25). In 1995, a Caucasian man with Fabry’s disease received a cadaveric renal transplant at Saint Barnabas Medical Center, Livingston, NJ. After immediate allograft function, spontaneous thrombosis of the transplant renal vein developed on postoperative day eleven. Subsequently, long-term allograft survival has been achieved by three consecutive recipients with Fabry’s disease at our center. Before 1990, diagnostic tests for hypercoagulability or thrombophilia included protein C deficiency (PCD), protein S deficiency (PSD), and antithrombin III deficiency (ATIII D). The diagnostic yield of these tests was low given the U.S. population incidence of 0.5, 0.003, and 0.001‐ 0.003%, respec