Background. Chronic allograft nephropathy (CAN) is the major cause of graft loss, and early detection is desirable to avoid irreversible graft damage. We have evaluated a new technique of color Doppler quantification using Cineloop (Philips Medical Systems, Bothell, WA) imaging for noninvasive diagnosis of CAN. Methods. Provisional normal ranges were defined by pilot study (n=13) and prospectively tested in stable recipients in whom CAN was independently quantified by contemporaneous histology (n=67), using the Banff schema. Results. The maximal fractional area (MFA, systolic color pixels/total area) was 28.7 +/- 9.7% in normal subjects and reduced to 18.8 +/- 8.0% in grade 1 and 12.5 +/- 6.4% in grade 2 CAN (both P < 0.001). The minimum color fractional area was reduced from 10.3 +/- 5.3% in normal subjects to 3.1 +/- 2.6% in grade 2 CAN (P < 0.001), but was less useful. Distance from peripheral color pixels to capsule increased in CAN grade 2 versus 0 (6.0 +/- 1.6 vs. 3.9 +/- 1.0 mm, respectively; P < 0.001). Calcineurin inhibitor nephrotoxicity reduced MFA (18.0 +/- 9.3 vs. 26.9 +/- 10.7%; P < 0.001) and other dynamic measurements. Parenchymal damage exerted minimal effect on resistance index, mean variance, and peak Doppler velocity. MFA (cutoff<17.3%) can diagnose CAN (sensitivity 69%, specificity 88%, positive predictive value 86%) and severe CAN (sensitivity 87%, specificity 71%, negative predictive value 95%). Distance to capsule >5 mm was less sensitive (49%) but more specific (91% alone, and 97% combined with MFA). Conclusions. In conclusion, quantitative Doppler ultrasound can reliably detect CAN and, although imperfect at correctly grading, allows recognition of significant tubulointerstitial damage for initiation of a confirmatory needle core biopsy.