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Blue light, but not green or red light, inhibited growth of retinal pigment epithelial (RPE) cells, aortic endothelial cells, and fibroblasts in vitro. Significant inhibition was observed in all 3 cell types exposed for 18 hr to blue light (425-500 nm) at 42 J/cm2. Damage was prevented by inclusion of superoxide dismutase (SOD) and catalase, providing evidence for a photooxidative mechanism. Dopa (100 microM) also caused oxidative damage that suppressed growth of all 3 cell types. A synergism of dopa and light effects was observed in endothelial cells and fibroblasts, but the agents caused additive effects on RPE cells. Endothelial cells were the most sensitive to dopa, light, and the two combined. Fibroblasts were the only cell type that exhibited greater sensitivity to light than to dopa. These data suggest that oxygen-mediated damage to the growing blood vessels in the retina of a premature infant may be exacerbated by exposure to blue light. A further implication is that restriction of RPE melanogenesis to the prenatal period of darkness and lower oxygen protects the retina from simultaneous oxidative challenge by light and by reactive species generated during oxidation of dopa released to the extracellular environment.