We studied five patients with multiple sclerosis with one plaque of demyelination more than 2 cm in diameter, using conventional and diffusion-weighted MRI, soon after the onset of symptoms and over 1-36 months. The orientationally averaged diffusion coefficient <D> was increased in all the acute lesions, and increased further during follow-up in three. There was a strong correlation between <D> and the degree of low signal on T1-weighted images. The quantitative information provided by <D> allowed delineation of different diffusion patterns in large MS lesions, that may reflect heterogeneity of the anatomical substrate.