The optimal therapeutic management of borderline lymphocytic infiltrates in renal allografts, described by Banff criteria, is unknown, largely because of the inability to predict clinical outcome in these cases. For determination of molecular factors that may predict outcome in cases of borderline change histology, mRNA levels of Foxp3, Granzyme B, IFN-gamma, IL-23, and RORgammat were measured in renal tissue from 46 untreated patients. Twenty-five patients were considered "nonprogressive," defined by a serum creatinine that remained <110% of baseline during the 40 d after biopsy. Twenty-one patients were considered "progressive," defined by an increase in serum creatinine >110% from baseline and by repeat histologic examination within 40 d showing progression toward acute rejection. Only Foxp3 mRNA levels were significantly higher in nonprogressors than in progressors (P = 0.001). Analysis of receiver operating characteristic curves demonstrated that the outcome for patients with biopsies showing borderline change could be predicted with 90% sensitivity and 79.1% specificity using the optimal Foxp3 mRNA cutoff value. Our findings suggest that the measurement of Foxp3 mRNA offers a means of improving prediction of outcome of borderline change.