PURPOSE. Acute optic neuritis (ON) is often followed by recovery of visual function. Although this recovery is mainly attributable to resolution of the acute inflammation, the redistribution of ion channels along the demyelinated membrane, and subsequent remyelination, part of it may be the result of neural plasticity. In the present study, the interrelationship was examined between structural (retinal nerve fiber layer [RNFL] thickness) and functional (amplitude of multifocal visual evoked potentials [mfVEPs]) measures of the integrity of the visual pathway in the postacute stage of ON, to determine whether there was any evidence of ongoing neural reorganization. METHODS. Twenty-five subjects with acute unilateral ON underwent serial RNFL thickness measurement and mfVEP recording. The inter-eye asymmetry of both measures was analyzed. In the period between 6 and 12 months, the subjects were considered free of optic disc edema, and that period was used to analyze the structure-function relationship. Twenty control subjects were also examined. RESULTS. There were significant but opposite changes in RNFL thickness and mfVEP amplitude. The average asymmetry of RNFL thickness between affected and fellow eyes increased from 17.5 ± 11.5 to 21.1 ± 12.8 μm (P = 0.0003), indicating progressive axonal loss, whereas mfVEP amplitude asymmetry decreased from 46.6 ± 32.4 to 38.3 ± 31.1 nV (P = 0.0015), indicating continuous functional recovery. In comparison to the 6-month results, the mfVEP amplitude in the ON eye improved by 17.8%, whereas RNFL thickness decreased by 20.8%. The result remained unchanged regardless of the degree of optic nerve remyelination. CONCLUSIONS. The finding of structural-functional discrepancy at the postinflammatory stage may support the concept that neural plasticity contributes to functional recovery after acute ON.