The aim of our work was to evaluate if an optic nerve involvement (multiple sclerosis patients previously affected by optic neuritis) may induce any change in visual evoked potential (VEP) after photostress response. VEP in basal conditions and after photostress were assessed in 10 patients with defined multiple sclerosis without a history of optic neuritis (MSWO); in 14 patients with defined multiple sclerosis previously affected by optic neuritis but with complete recovery of the visual acuity (MSON) and in 14 age-matched controls. In order to complete the investigation of the retinal function, Transient Pattern electroretinogram (PERG) and steady-state focal-ERG (counterphased gratings presented at 8 Hz in the macular region) were performed in MSON patients only. In MSWO eyes VEP parameters in basal condition and after photostress did not undergo significant changes compared to controls (ANOVA; P > 0.05). In MSON eyes we observed basal VEP with delayed P100 peak latency and reduced N75-P100 amplitude when compared with the control ones (P < 0.01). In MSON eyes the parameters of VEP after photostress underwent large changes and longer recovery time (RT) than in control and MSWO eyes (P < 0.01). In addition; in MSON eyes we found increased transient PERG P50 latency (P < 0.01) and reduced P50-N95 amplitude (P < 0.01); Focal-ERG (that displays a major component at 16 Hz; 2nd harmonic:2P) with reduced 2P amplitudes and delayed 2P phases (P < 0.01). Our results indicate that patients previously affected by optic neuritis present an abnormal VEP after photostress response and this may be ascribed predominantly to an involvement of the inner retinal layers as indicated by the concomitant impairment of PERG and focal-ERG responses.