Diffusion-weighted imaging (DWI) provides a unique form of magnetic resonance (MR) contrast that enables the diffusional motion of water molecules to be quantitatively measured. As a consequence, DWI provides information about the orientation, size and geometry of brain structures. Cellular structures in the central nervous system restrict water molecular motion, and the apparent diffusion coefficient (ADC) is reduced compared to diffusion in bulk water. Pathological processes that modify tissue integrity, thus removing some of the "restricting" barriers, can result in increased ADC. Preliminary studies in multiple sclerosis (MS) using DWI showed that the ADC is higher in macroscopic lesions than in the normal appearing white matter (NAWM). The ADC is also dependent on the direction in which diffusion is measured, thus making comparison of ADC values meaningless without taking into account the measurement direction. One measurement of diffusion that is independent of the orientation of structures is provided by measuring the ADC in three orthogonal directions, and then averaging the results to form the mean diffusivity, D. We obtained DW scans from 35 patients with relapsing-remitting MS and 24 healthy volunteers. D was measured inside T2-visible lesions and regions located in different areas of the NAWM. D histograms from a large portion of the brain were created. MS lesions had a significantly higher D than NAWM. T1-hypointense lesions had the highest diffusion values, consistent with more severe tissue disruption. D was higher in the NAWM from patients than in the white matter from healthy controls. We also found significant differences between D histogram-derived measures from patients and controls, confirming the presence of diffuse damage in the brain of patients with MS.