Recent evidence indicates that the 2nd harmonics of steady-state (8 Hz) electroretinograms to either sinusoidal flicker (FERG) or to counterphased gratings (PERG) presented in the macular region (9 degrees) represent different subsets of generators in the inner retina. We evaluated the steady-state macular FERG and PERG 2nd harmonics (2F and 2P, respectively) in 19 normal subjects (19 eyes) and in 23 multiple sclerosis patients (44 eyes; 25 eyes with a history of clinical optic neuritis, and 19 eyes with no history of optic neuritis, subclinical eyes). The mean 2F and 2P amplitudes were significantly reduced, as compared to controls, in both subclinical and optic neuritis eyes. The 2P phase was significantly delayed, as compared to controls, in subclinical eyes, whereas 2F phase was delayed in eyes with optic neuritis. 2F was outside the 95% confidence limits (in amplitude or phase) in 11/19 subclinical eyes and in 25/25 optic neuritis eyes. 2P was outside the normal range in 12/19 subclinical eyes and in 24/25 optic neuritis eyes. These results show that FERG and PERG 2nd harmonics are significantly altered in multiple sclerosis eyes with or without a clinical history of optic neuritis. This finding suggests a dysfunction of inner macular layers which may result from direct retinal involvement or retrograde degeneration.