After the oral ingestion of sildenafil, visual abnormalities have been reported constantly. The mechanism of these adverse events has been presumed to be a result of the interaction of sildenafil with the retinal phosphodiesterase (PDE) type 6. To investigate the physiological basis of the effects of sildenafil on retinal function, bovine retinas were isolated and perfused with an oxygen pre-equilibrated standard solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver-chloride electrodes. After reaching stable ERG amplitudes, sildenafil was added to the nurient solution at different concentrations, and its effect on the a- and b-wave amplitude was studied separately. The 0.1 microM and higher concentrations of sildenafil reduced the b-wave amplitude, while a reduction of the a-wave amplitude was observed at an elevated threshold of 0.3 microM. The changes of the ERG amplitudes were fully reversible for the b-wave at a concentration of 0.1 microM and for the a-wave at 0.3 microM sildenafil. At higher concentrations, sildenafil was found to be only partially reversible within recovery time. In conclusion, besides an inhibitory influence on photoreceptors, sildenafil performs additional effects on the postsynaptic neuronal network. Higher concentrations of sildenafil were found to have a potential for retinal degeneration, suggesting that further trials should be designed to evaluate the long-term effects of sildenafil. The physiological consequences of an abuse or long-term, daily use of sildenafil are not clear.