Quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) provides estimates of physiologically relevant parameters related to tissue blood flow, vascular permeability, and tissue volume fractions which can then be used for prognostic and diagnostic reasons. However, standard techniques for DCE-MRI analysis ignore intra-voxel diffusion, which may play an important role in contrast agent distribution and voxel signal intensity and, thus, will affect quantification of the aforementioned parameters. To investigate the effect of intra-voxel diffusion on quantitative DCE-MRI, we developed a finite element model of contrast enhancement at the voxel level. For diffusion in the range of that expected for gadolinium chelates in tissue (i.e., 1 × 10(-4) to 4 × 10(-4) mm(2)/s), parameterization errors range from -58% to 12% for K(trans), -9% to 8% for ve, and -60% to 213% for vp over the range of K(trans), v(e), v(p), and temporal resolutions investigated. Thus the results show that diffusion has a significant effect on parameterization using standard techniques.