OBJECTIVE Prior clinical observations led the authors to examine electrophysiologic measures of retinal (electroretinogram [ERG]) and retinal pigment epithelial (electro-oculogram [EOG]) function in patients infected with human immunodeficiency virus (HIV) who either had or did not have cytomegalovirus (CMV) retinitis in order to determine if the ERG or EOG measures were differentially affected in CMV retinitis. METHODS Cross-sectional study. METHODS Forty-one HIV-infected patients (20 with and 21 without CMV retinopathy) were evaluated. METHODS ERGs and EOGs were recorded. Patients' fundi were evaluated by indirect ophthalmoscopy or fundus photography. METHODS The ERG a- and b-wave amplitudes and EOG light/dark amplitude ratio (L/D ratio) from the eyes of all patients were compared with values 2 standard deviations from the mean of a normal sample. The area of the retinal lesions was estimated from fundus photographs or from careful drawings made during indirect ophthalmoscopy. RESULTS The majority of the eyes (64.5%) of the patients with CMV retinitis had subnormal L/D ratios, and most eyes (95%) of patients without CMV retinitis had normal L/D ratios. Only six eyes (four with and two without CMV retinopathy) had subnormal a-wave amplitudes, and there was no significant correlation between a-wave amplitude and the L/D ratio for patients with CMV retinitis. Most eyes (80.6%) of the patients with CMV retinitis had subnormal b-wave amplitudes, but there was no significant correlation between b-wave amplitude and L/D ratio in the patients with CMV retinitis. In three patients with CMV retinitis selected to exemplify the range of effects on the ERG and EOG, the b-wave amplitude loss was roughly proportional to the area of retina visibly affected in indirect ophthalmoscopy. One patient had a nonrhegmatogenous retinal detachment. CONCLUSIONS Middle retinal function, as reflected in the b-wave amplitude, and retinal pigment epithelial function, as reflected in the L/D ratio, were both compromised in CMV retinitis, but the effect on function in the two layers of the retina appeared independent because there was no significant correlation between the L/D ratio and b-wave amplitude. The decrease in L/D ratio was not secondary to loss of photoreceptor function and probably represents a dysfunction of the retinal pigment epithelium because there was no significant correlation between a-wave amplitude, which was normal in most cases, and L/D ratio. The inner retinal pathology of CMV retinitis is visible clinically and was associated with decreases in b-wave amplitude in this and previous studies. The significant independent retinal pigment epithelial dysfunction demonstrated in this study may be an important predisposing factor to retinal detachment in CMV retinitis.