As it is known that chlorpromazine (CPZ) can bind to melanins as well as cause ocular phototoxicity, we investigated the cytotoxic effects of UV-visible irradiation of melanotic and amelanotic retinal pigment epithelial (RPE) cells in the presence of CPZ. At low concentrations (5μg/ml) of CPZ a photosensitization reaction took place which lysed the cell is as measured by the release of51Cr from cells labelled with chromium. At concentrations of CPZ less than 5μg/ml, no significant cell lysis occurred when the cells were incubated at 37°C in the dark. As the concentration of CPZ was increased to 25μg/ml or more, high percentages of cells were lysed. When the melanotic RPE cells were exposed to different concentrations of CPZ and grown in culture, the cell growth (multiplication) diminished drastically with low concentrations (less than 2μg/ml CPZ). Vitamin E decreased the eel 1 lysis both in the dark and upon irradiation. Oxygen radical scavengers such as glutathione, B-carotene, mannitol, D-penicil lamine as well as superoxide dismutase and catalase did not decrease cell lysis. The phototoxic effects of CPZ was found not to be due to stable photoproducts formed during irradiation of CPZ.