After renal transplantation low urinary sodium concentration (UNa) has been used to diagnose acute rejection (AR), for the early phase of AR is often associated with reduced renal perfusion. Early postoperative graft failure without low UNa favors the diagnosis of ischemic tubular damage (ATN). As fractional excretion of filtered sodium (FENa) better reflects glomerulotubular balance in renal sodium handling, FENa was analyzed during the first 2 weeks in 118 renal allografts. From data on 41 transplants with good early renal function (GEF), a temporal profile of FENa was obtained and used to evaluate the behavior of FENa by means of standardized FENa (Z score). Individual subjects followed their own profile with a small deviation (delta Z less than 1.4 for 2 days). In 31 instances, acute rejection was diagnosed. In 14 with AR, the Z score deviated little; 2 responded to methylprednisolone given intravenously. In 17 with AR, the Z score fell significantly (delta Z greater than 1.5 for 2 days), an average of 2.6 days before the first rise in serum creatinine concentration; 15 responded to treatment. The difference between these two groups was significant (P less than 0.001). This functional heterogeneity and different responses to treatment may indicate different immunologic mechanisms which damage different target cells in the graft in AR. In 46 patients with acute tubular necrosis after cadaver kidney transplantation FENa was significantly higher than it was in the GEF group as early as the first posttransplantation day and approached normal as the renal function recovered. This behavior of FENa was clearly different from that in AR.