Models have been developed for analyzing dynamic contrast-enhanced (DCE)-MRI data that do not require measurements of the arterial input function (AIF). In this study, experimental results obtained from a reference region (RR) analysis are compared with results of an AIF analysis in the same set of five animals (four imaged twice, yielding nine data sets), returning estimates of the volume transfer constant (Ktrans) and the extravascular extracellular volume fraction (ve). Student'st-test values for comparisons of Ktrans and ve between the two models were 0.14 (P= 0.88) and 0.85 (P> 0.4), respectively (where the highP-values indicate no significant difference between values derived from the two models). Linear regression analysis indicated there was a correlation between Ktrans extracted by the two methods: r2 = 0.80,P= 0.001 (where the lowP-value indicates a significant linear correlation). For ve there was no such correlation (r2 = 0.02). The mean (absolute) percent difference between the models was 22.0% for Ktrans and 28.1% for ve. However, the RR parameter values were much less precise than the AIF method. The mean SDs for Ktrans and ve for the RR analysis were 0.024 min–1 and 0.06, respectively, vs. 0.002 min–1 and 0.03 for AIF analysis. Magn Reson Med 57:353–361, 2007. © 2007 Wiley-Liss, Inc.