PURPOSE. To examine the natural history of multifocal visual evoked potentials (mfVEPs) within 12 months of the first episode of optic neuritis (ON) in patients with possible multiple sclerosis (MS). METHODS. Twenty-seven patients with a first episode of ON, no previous demyelinating events, and MRI lesions consistent with demyelination were examined with mfVEP. Changes in amplitude and latency of mfVEP were analyzed at 1, 3, 6, and 12 months after an acute attack. RESULTS. Five of 27 patients had persistent loss of amplitude after 12 months of follow-up. This loss was most marked centrally. Amplitude recovered in the remaining 22 patients at 1 month, but delayed latency, which was also most marked centrally, persisted. Of these, two distinct subgroups were identified: six patients with no improvement in latency and 16 patients with significant latency recovery over the 12 months of follow-up, suggesting remyelination. Conversion to MS was highest in the group with severe amplitude loss, followed by the group with no latency recovery. The conversion rate was lowest in the group of patients with latency improvement. CONCLUSIONS. Distinct patterns of disease evolution were identified using mfVEP in patients with first episode of optic neuritis and at high risk for MS, supporting the concept of heterogeneity of early lesions in MS.