We evaluated the effects of retinal diseases on the macular electroretinogram first and second harmonic components, which are dominated by outer and inner retinal activity, respectively. Macular electroretinograms in response to a uniform field (9 degrees x 9 degrees) flickering sinusoidally at either 32 or 8 Hz (peak frequencies of the first and second harmonics, respectively) were recorded in 14 patients with maculopathies involving photoreceptors (e.g., age-related macular degeneration), in 16 patients with postreceptoral macular diseases (e.g., branch occlusion of central retinal artery), and in 38 normal controls. Amplitude and phase of the first and second harmonic response components were evaluated by Fourier analysis. When compared to controls, patients with photoreceptor diseases had reduction in both first and second harmonic mean amplitudes and second harmonic phase delay; patients with postreceptoral diseases had normal first harmonic components but reduced and delayed second harmonic components. A discriminant analysis, by using first and second harmonic values, correctly classified 13 of 14 patients with photoreceptor diseases and 14 of 16 patients with postreceptoral disorders. These results indicate that combined evaluation of the macular electroretinogram first and second harmonic components is a useful test for identifying the site(s) of retinal dysfunction in patients with macular diseases.