111In-labeled platelet scintigraphy was used to confirm immunological intolerance as the cause of prolonged febrile syndrome in hemodialyzed patients with a nonfunctioning renal allograft. Thirty-six patients with febrile syndrome (> 38 degrees C) and a nonfunctioning renal graft were studied. Thirteen patients were under minimal steroids (5-10 mg/day) and 23 were free of immunosuppressive therapy. A control group of 6 patients without fever and with a nonfunctioning renal graft was also included. The labeling of autologous platelets with 111In-mercaptopyridine was performed following a modified technique of Thakur. Scans were obtained at 24 and 48 hr after injection of 100-200 microCi of 111In-labeled platelets. A platelet uptake index (PUI) was calculated to evaluate the results of the scintigraphy. A PUI > 1.5 at 24 or 48 hr was considered positive and suggestive of immunological activity in the nonfunctioning renal allograft. In the study group the PUI was considered positive in 26 patients and negative in 10. In 3 patients with positive PUI, fever disappeared after steroid treatment, and transplantectomy was performed in the remaining 23. In 8 of the 10 patients with a negative PUI, fever disappeared with antimicrobial therapy. In the control group, a negative PUI was obtained in all cases. The sensitivity of PUI in demonstrating immunological intolerance of the nonfunctioning renal allograft was 93% with a specificity of 100%. Our results suggest that this new approach with 111In-labeled platelet scintigraphy may constitute a good marker for discriminating the origin of the febrile syndrome in patients with a nonfunctioning renal allograft. A positive PUI (> 1.5) strongly suggested immunological intolerance of the nonfunctioning allograft.