Muscles of myositis patients examined with MRI demonstrate heterogeneous pathology ranging from unaffected muscle groups to severe inflammation, fat infiltration, and eventually, more serious fat replacement. The purpose of this investigation was to characterize myositic thigh muscles using diffusion-weighted imaging (DWI) and to examine fluid motion at various disease stages. We chose to characterize total fluid motion within the muscle using the model proposed by Le Bihan et al (6,7) in which the apparent diffusion coefficient (ADC), diffusion in the extra- and intracellular muscle compartments (D), perfusion in capillaries (pseudodiffusion) (D*), and volume fraction of capillary perfusion (f) are determined. Unaffected patient muscles have DWI coefficients equivalent to those of normal muscles. Inflamed muscles show elevated ADC and D values compared to normal muscles (P < 0.0005), and fat-infiltrated muscles have lower values than control muscles (P < 0.001). Inflamed muscles have lower f values than unaffected muscles (P < 0.009), suggesting decreased fractional volume of capillary perfusion. DWI provides quantitative data on molecular fluid motion in diseased muscles and affords the potential for longitudinal monitoring of myositic patients.