BACKGROUND We investigated the diagnostic and prognostic value of urinary programmed death 1 (PD-1) and FOXP3 (Forkhead transcription factors) mRNA in acute renal allograft rejection. MATERIAL AND METHODS Urine samples from 31 acute renal allograft rejection subjects and 23 stable recipients were collected. Messenger RNA of PD-1 and FOXP3 were analyzed with real-time RT-PCR. The associations with acute rejection, disease severity, and outcome were investigated. RESULTS Both PD-1 and FOXP3 mRNA were higher in acute rejection than subjects with stable grafts. In acute rejection, PD-1 and FOXP3 mRNA were significantly correlated with serum creatinine and Banff histological grade. Both PD-1 and FOXP3 mRNA performed well in diagnosing acute rejection (AUC 0.81 and 0.91, respectively). However, a combination of both FOXP3 mRNA at cutoff level 1.5 and PD-1 mRNA at cutoff level 2.6 had 94% sensitivity, 97% specificity, and AUC 0.98 in diagnosing acute rejection. Only FOXP3 mRNA was correlated with rejection reversibility and predicted graft salvage (98% sensitivity, 87% specificity, and AUC 0.93) at cutoff level 1.7. CONCLUSIONS PD-1 and FOXP3 mRNA were high in acute rejection, and performed well in diagnosing rejection episodes, and were correlated with rejection severity. The combination of FOXP3 and PD-1 mRNA had better sensitivity and specificity in diagnosing acute rejection than each separately. Only FOXP3 anticipated rejection outcome.