The direct current electroretinogram (ERG) and the standing potential (SP) were recorded from both eyes of 14 albino rabbits during intraocular perfusion of one of the eyes, which was vitrectomized, with a recently developed eye irrigation solution (PHS) produced by Pharmacia Ophthalmics. PHS was then replaced by a test solution containing melatonin dissolved in PHS (0.002 microM-200 microM). The fluids were subsequently alternated (PHS - melatonin - PHS). During uniocular irrigation with melatonin the mean c-wave amplitude and SP level of the intact control eye were increased (c-wave +24%, p less than 0.01; SP +0.65 mV, p less than 0.05) compared with the values during the initial perfusion with PHS. In contrast, the c-wave amplitude of the irrigated eye was markedly decreased in many rabbits during perfusion with melatonin compared with the initial PHS, but the mean reduction was small and not statistically significant. The mean SP level was reduced (-1.54 mV, p less than 0.001). This difference between the eyes probably depends on the route by which melatonin reaches the retinal pigment epithelium and thus whether it primarily affects the apical (as in the irrigated eye) or the basal (as in the control eye) pigment epithelial membrane. A peak in the b-wave amplitude was observed in both eyes during uniocular irrigation with melatonin when compared with the amplitude measured during the initial perfusion with PHS (irrigated eye: +27%, p less than 0.001; control eye +18%, p less than 0.002).