Because demyelinating disease of the brain occasionally presents with large ring-enhancing lesions on computed tomography (CT) scans and magnetic resonance images (MRIs), the authors sought to determine whether the ring pattern differed from that found in other common brain lesions with ring enhancement. Published MRI and CT scans of patients with adrenoleukodystrophy (23), and multiple sclerosis or similar demyelinating disorders (21), as well as a variety of tumors (44) and infections (44) matched to the demyelinating lesions by year of publication, in which ring enhancement was evident, were photographed. Photographs without diagnostic identification were presented randomly to two independent observers. The observers rated the contrast enhancement pattern as (1) open ring, with enhancement in the border of the lesion abutting the white matter; (2) closed ring; or (3) uncertain. For all diagnostically certain cases (n = 112), inter-rater agreement was excellent (kappa = 0.75). As an average of the two reviewers, scans for 11 of 132 cases were read as uncertain; 89% of adrenoleukodystrophy cases, 41% of the multiple sclerosis cases, 3% of tumors, and 9% of infections were classified as having the open-ring pattern. Overall, 66% of demyelinating lesions had an open-ring pattern compared with 7% of the non-demyelinating lesions (chi2 = 41.2, p< 0.0001). An open-ring pattern of enhancement is more likely to be associated with demyelinating lesions than with nondemyelinating lesions.