Magnetic resonance imaging (MRI) with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) was used to investigate disruption of the blood-optic nerve barrier associated with acute autoimmune demyelination. Leakage of Gd-DTPA was seen in the optic nerves and optic chiasm of adult guinea pigs sensitized for acute experimental allergic encephalomyelitis, but not in normal unsensitized animals. This finding occurred as early as 5 to 8 days after antigenic sensitization with the myelin emulsion and before the onset of paralysis or ataxia. Pathologic examination at this early stage of experimental allergic encephalomyelitis showed an absence of demyelination in the optic nerves and optic chiasm, although scant perivascular foci of inflammatory cells were seen. Leakage of Gd-DTPA in the optic nerve before demyelination of this white matter tract illustrates that increased permeability of the blood-optic nerve barrier is an early, if not the initial, event in autoimmune demyelination, and the optic nerve is a common site of central nervous system involvement during the initial phase of acute experimental allergic encephalomyelitis. Findings in this animal model appear comparable with the results of MRI with Gd-DTPA in patients with optic neuritis, and they suggest that disruption of the blood-optic nerve barrier is a common denominator for both disorders of primary demyelination.