Increased blood-brain barrier (BBB) permeability, important in the pathogenesis of MS, may be demonstrated as lesion enhancement with high-volume delayed CT (HVDCT). We studied 40 MS patients with history, neurologic examination, HVDCT, and MRI. In addition, 7 of the patients with enhancing CT lesions were followed with serial MRI for up to 3 years and 7 months. In 3 of these patients we repeated the HVDCT. Patients with enhancing lesions on CT were younger, had shorter duration of disease, and had more frequent clinical relapses than did patients without enhancement. More than half (56%) of the enhancing CT lesions were in the deep white matter, 23% were periventricular, and 21% were at the gray/white matter junction. Half the CT enhancing lesions, when followed by serial MRI, showed significant changes in lesion size. Although the majority (59%) of these lesions faded, some remained actively changing (25%) or became confluent with adjacent lesions (16%). In 48% of the MRI examinations that showed activity, some lesions were increasing in size while others were simultaneously decreasing in size. This study confirms that MS is a dynamic process in which recurrent episodes of BBB disruption and inflammation play a major role. Recurrent episodes of inflammation may well be a prelude to the largely irreversible changes of demyelination and gliosis.