The purpose of this study was to evaluate the usefulness of labelled platelet scintigraphy in the differential diagnosis of a prolonged febrile syndrome (PFS) in patients on dialysis carrying a non-functioning renal allograft. We prospectively performed an indium-111 mercaptopyridine-labelled platelet scan on 91 patients (54 men, 37 women; mean age 39.6+/-12 years). The mean duration of PFS was 35 days (range 7-122). Forty-six of the 91 patients underwent steroid therapy (2-10 mg/day). Platelet labelling was carried out following Thakur's method. Platelet scans were performed 48 h after reinjection of labelled platelets. The platelet uptake index (PUI) was calculated by dividing the cpm/pixel in the allograft ROI by cpm/pixel in a mirror background ROI. The final diagnosis of PFS was established depending on the outcome after treatment. In 61/91 patients the fever had an immunological origin because it disappeared after graft embolisation or transplantectomy. In 30/91 patients the PFS disappeared after antibiotic therapy (non-immunological origin). The PUI in patients with immunological PFS was 1.80+/-0.7, while in patients with non-immunological PFS it was 1.12+/-0.1 (P<0.05). When a PUI of > or =1.5 was considered as the threshold to establish PFS of immunological origin, the sensitivity of platelet scan was 76%, the specificity 100%, and the negative and positive predictive values 69% and 100%, respectively. In patients classified with immunological PFS who underwent steroid therapy, the PUI was significantly lower than in patients without steroids (P<0.05). These results suggest that 111In-labelled platelet scintigraphy can accurately predict an immunological PFS in patients on dialysis carrying a non-functioning renal allograft. Therapy with steroids could reduce the sensitivity of 111In-labelled platelet scintigraphy in detecting immunological PFS.