A number of two-compartment models have been developed for the analysis of arterial spin labeling (ASL) data, from which both cerebral blood flow (CBF) and capillary permeability-surface product (PS) can be estimated. To derive values of PS, the volume fraction of the ASL signal arising from the intravascular space (v(bw)) must be known a priori. We examined the use of diffusion-weighted imaging (DWI) and subsequent analysis using the intravoxel incoherent motion model to determine v(bw) in the human brain. These data were then used in a two-compartment ASL model to estimate PS. Imaging was performed in 10 healthy adult subjects, and repeated in five subjects to test reproducibility. In gray matter (excluding large arteries), mean voxel-wise v(bw) was 2.3±0.2 mL blood/100 g tissue (all subjects mean±s.d.), and CBF and PS were 44±5 and 108±2 mL per 100 g per minute, respectively. After spatial smoothing using a 6-mm full width at half maximum Gaussian kernel, the coefficient of repeatability of CBF, v(bw) and PS were 8 mL per 100 g per minute, 0.4 mL blood/100 g tissue, and 13 mL per 100 g per minute, respectively. Our results show that the combined use of ASL and DWI can provide a new, noninvasive methodology for estimating v(bw) and PS directly, with reproducibility that is sufficient for clinical use.