Hypericin is an important component of the Saint John's wort (Hypericum perforatum). It is assumed to inhibit intracellular signalling cascades, which contribute to neoangiogenesis. The phototoxic effect of hypericin on the retina was investigated in human retinal pigment epithelium (RPE); hypericin induces oxidative stress and has also been described to be an inhibitor of Ca(2+) influx channel in cultured RPE cells. The aim of our study is to evaluate the effect of hypericine on the function of the neuroretina. Isolated bovine retinas were perfused with an oxygen saturated nutrient solution (1 mL/min). We exposed the retina to a flashlight of 6.3 mlx every 5 min. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. ERGs were monitored before, during and after hypericin exposure. In three independent experiments we investigated the effect of hypericin on the amplitude of the b-wave. In our experiments we observed a significant reduction of the amplitude of the b-wave to 87.1 ± 3.5 % (p = 0.02). This reduction was in all our experiments partially reversible. After hypericin wash-out the b-wave amplitude did not recover completely and did not return to the initial value (91.0 ± 5.1 %; not significant). We did not observe a significant effect of hypericin on the implicit time of the b-wave. This study shows for the first time that hypericin influences retinal signal transduction, suggesting that hypericin impairs not only the RPE, but also affects retinal signalling and function.