We describe a novel method for the calculation of endothelial permeability surface area product from dynamic contrast enhanced MRI. The technique uses iterative estimation to automatically decompose tissue residue function into intravascular and extravascular components, which are subsequently used to generate tumour blood volume, which is equal to relative cerebral blood volume calculated from T(1) weighted images and corrected for contamination by contrast agent leakage (rCBV(T1)(corrected), and endothelial permeability (k(fp)) maps. The technique was assessed in patients with cerebral glioma (n=5) by examining the reproducibility of endothelial permeability and rCBV(T1)(corrected) between two separate examinations conducted with a 2-day interval. The technique produces maps of endothelial permeability that appear to be free of any contribution from intravascular contrast agent. Maps of rCBV(T1)(corrected) show close correlation with maps of blood volume calculated from independently acquired dynamic susceptibility weighted MRI examinations, with no evidence of residual permeability effects. The results were highly reproducible with strong intra-class correlation between the two examinations for mean values and for 97.5 percentiles of endothelial permeability and rCBV(T1)(corrected). The excellent reproducibility of this technique and the ability to calculate endothelial permeability and rCBV(T1)(corrected) values from rapidly acquired data sets offer considerable advantages over conventional approaches and support the use of this methodology for therapeutic monitoring or trials of novel therapeutic agents.