Chronic allograft nephropathy (CAN) is a major problem in posttransplant management. The lack of a reliable and early surrogate marker of CAN has hampered patient care and research. In this study, the Cortical Fractional Interstitial Fibrosis Volume (V(IntFib)), quantitated with computerized image analysis of Sirius Red-stained protocol biopsies, was examined as a potential surrogate for time to graft failure (TTGF) in 68 renal allograft recipients. At 6 mo posttransplant, V(IntFib) was highly correlated with TTGF (r = 0.64, P < 0.001). Both the Banff Chronic Sum and the Acute Sum Scores were also correlated with TTGF, but less strongly (r = 0.28, P < 0.02; r = 0.35, P < 0.003, respectively). As V(IntFib) was not correlated with the Banff Chronic Score, a multivariate model was created that incorporated V(IntFib) and both Acute and Chronic Banff pathology. This model was highly correlated with TTGF (r = 0.7, P < 0.0001). These findings suggest that V(IntFib) determined by computerized image analysis of Sirius Red-stained protocol biopsies at 6 mo posttransplant, with or without incorporation of Banff acute and chronic scoring, may provide an early surrogate for time to graft failure in renal allograft recipients.