To provide magnetic resonance imaging (MRI)-ultrastructural correlations of demyelinating lesions of the intraorbital optic nerve, the authors performed gadolinium-enhanced/T2-weighted fat-suppressed MRI and transmission electron microscopy of the optic nerves of animals with experimental allergic encephalomyelitis. Gadolinium enhancement of the optic nerve adjacent to the globe was seen on fat-suppressed T1-weighted MRI as early as 3 days after antigenic sensitization, increased in severity involving longer segments of nerve at 10 to 14 days, and persisted at 30 days. Gadolinium enhancement preceded T2-weighted signal aberrations. Ultrastructural evaluation of the intraorbital nerve revealed: (1) expansion of the extracellular space and inflammatory infiltrate that correlated with the intensity of gadolinium enhancement; (2) the degree of demyelination correlated with T2-weighted signal aberrations; (3) as deduced from gadolinium enhancement and T2 signal aberrations, breakdown of the blood-brain barrier preceded widespread demyelination; (4) lesions appeared to start at the optic nerve insertion into the globe and then progress toward the orbital apex.