Abstract: Oxidative damage to retinal cell membranes can lead to sight-threatening ocular diseases. Pineal indoleamines are naturally located and synthesized in the retina, and they possibly protect the retina from oxidative cell damage. In this study, we compared the efficacy of three different pineal indoleamines (melatonin, N-acetylserotonin, and pinoline) with vitamin E, a well-known antioxidant, against nitric oxide (NO)-induced lipid peroxidation (LPO) in rat retinal homogenates. The possible synergistic effect of these agents was also studied. Retinal homogenates were incubated with sodium nitroprusside, which releases NO'. The LPO product, malondialdehyde (MDA), provided an index of cell damage. The results show that vitamin E and indoleamines significantly reduced MDA levels in a dose-dependent manner. When vitamin E was combined with the indoleamines, the protection was synergistically enhanced. In summary, under conditions where cellular homogenates are used (a) vitamin E and the three pineal indoleamines protected the retinal cells from NO-induced LPO damage; (b) the efficacies of each of these compounds had the following relationships: vitamin E > N-acetylserotonin > pinoline > melatonin; (c) vitamin E acted synergistically with indoleamines in combating oxidative retinal damage. Whether these same associations would exist in vivo after treatment with these compounds is unknown. The pharmacological potential of indoleamines, possibly in combination with vitamin E, in preventing retinal pathogenesis deserves further investigation.