The incidence of acute tubular necrosis (need for hemodialysis immediately after transplantation) and its severity (the number of days dialysis was needed) were studied in 299 patients who were randomized prior to transplantation into undergoing splenectomy or not having splenectomy. There was no difference in the incidence of acute tubular necrosis between splenectomized and nonsplenectomized patients who received cadaveric grafts or kidneys from living related donors. In those patients in the cadaveric group who had acute tubular necrosis, the duration of need for dialysis was significantly less (p < 0.05) in the splenectomized group (x = 8.9 days) when compared to the nonsplenectomized group (x = 13.2 days). Animal experiments indicate that sustained prostaglandin release may be responsible for the decreased incidence and amelioration of acute tubular necrosis in splenectomized animals. Our study suggests that conclusions made in dogs about the influence of splenectomy on acute tubular necrosis may be applied to humans. Prostaglandin infusion may be a worthwhile method to abolish or ameliorate human acute tubular necrosis.