Magnetic resonance imaging (MRI) is widely used to evaluate and monitor disease activity in inflammatory demyelinating central nervous system (CNS) diseases such as multiple sclerosis. The present study aimed at correlating MRI findings with histological parameters in 6 cases of biopsy-proven inflammatory demyelination of the CNS. The earliest stages of demyelinating activity manifested as almost isointense lesions with a massive gadolinium-DTPA (Gd-DTPA) enhancement in T1-weighted scans. In T2-weighted scans, early active lesions formed a border of decreased intensity compared with the lesion center and the perifocal edema. The morphological correlate of this pattern in our patients was activated macrophages in the zone of myelin destruction at the plaque border. Late active lesions were hypointense in T1 and hyperintense in T2 scans. Inactive demyelinated and remyelinating lesions were hyperintense in T2 scans and enhanced inhomogenously after Gd-DTPA application. T1 scans revealed major differences in the degree of hypointensity that correlated with the extent of axonal damage, extracellular edema, and the degree of demyelination or remyelination.