We evaluated short- and long-term effects of high-dose recombinant human erythropoietin (rHuEPO) in kidney transplantation in a prospective double-blind, placebo-controlled study. Patients with chronic kidney disease following receipt of a deceased donor kidney allograft were randomized to 3 doses of 40,000 units rHuEPO or placebo. The primary study end point was kidney function 6 weeks after transplantation with secondary end points of incidence of delayed graft function and kidney function 12 months after transplantation. Six weeks or 12 months after transplantation, the difference between estimated glomerular filtration rates was not significant comparing 44 patients who received rHuEPO to 44 patients receiving placebo. There was no significant difference regarding the incidence of delayed graft function (10 of 44 with rHuEPO compared with 14 of 44 on placebo). Protocol biopsies at 6 weeks and 6 months post transplant showed no significant differences in all assessed histological indices. The number and severity of adverse events were comparable between groups, as was patient and graft survival after 12 months. Thus, treatment with high-dose rHuEPO after kidney transplantation, although well tolerated, had no effect on long-term graft function or histology.