Objective: To investigate the relation between retinal nerve fiber layer (RNFL) thickness and latency and amplitude of multifocal visual-evoked potentials (mfVEPs) in the postacute stage of optic neuritis in patients with early or possible multiple sclerosis. Method: Thirty-two patients with clinical diagnosis of unilateral optic neuritis and magnetic resonance imaging lesions typical of demyelination and 25 control subjects underwent mfVEP and optical coherence tomography imaging. Results: Although there was significant reduction of RNFL thickness in the affected eyes (18.7%), a considerably larger decrease was observed for the amplitude of the mfVEPs (39.8%). Latency of the mfVEPs was also significantly delayed in optic neuritis eyes. In fellow eyes, the amplitude of mfVEPs was significantly reduced and the latency prolonged, but RNFL thickness remained unaltered. RNFL thickness correlated highly with the mfVEP amplitude (r = 0.90). There was also strong correlation between optical coherence tomography measure of axonal loss and mfVEP latency (r = -0.66). Interpretation: Although our findings demonstrate strong associations between structural and functional measures of optic nerve integrity, the functional loss was more marked. This fact, together with amplitude and latency changes of the mfVEPs observed in clinically normal fellow eyes, may indicate greater sensitivity of mfVEPs in detecting optic nerve abnormality or the presence of widespread inflammation in the central nervous system, or both. The significant correlation of the mfVEP latency with RNFL thickness suggests a role for demyelination in promoting axonal loss.