OBJECTIVE Previous studies have shown that ingestion of fish oil (FO) containing a high proportion of n-3 polyunsaturated fatty acids increases the susceptibility of cellular membranes to oxidative damage in various tissues. In the retina, lipid peroxidation is thought to be a major mechanism contributing to light-induced lesions. Therefore, we investigated the effect of FO on acute light-induced photoreceptor damage. METHODS For 2 months, weanling rats were fed diets containing either soybean oil (SOY) or FO as main lipid component. RESULTS Rats fed FO had significantly higher levels of eicosapentaenoic acid (EPA, 20:5n-3) and higher ratios of EPA to arachidonic acid (AA, 20:4n-6) in retinal phospholipids and diacylglycerols than rats fed SOY. The levels of docosahexaenoic acid (DHA, 22:6n-3) were similar in both dietary groups. The susceptibility to lipid peroxidation was enhanced in the isolated retina of FO-fed rats as shown by higher levels of thiobarbituric acid reactive substances after incubation of retinal membranes with Fe2+/ascorbate. The retinal content of alpha-tocopherol was similar in SOY- and FO-fed animals. Light damage consisting of acute rod outer segment (ROS) disruptions was induced by exposing dark-adapted animals to 600 to 700 lux (230 to 260 microW/cm2) of white fluorescent light for 30 minutes. Damage was quantitated using a computerized multifunctional image analysis of retinal thin sections. Although structural alterations of the ROS were present in both groups, FO-fed rats showed less damage at the base of the ROS. This occurred in spite of higher rhodopsin levels in FO-fed rats. There was no effect of diet on retinal morphology in dark-adapted rats. CONCLUSIONS These results indicate that FO does not enhance the susceptibility to acute ROS disk disruptions in the rat retina. Our study further suggests that FO exerts a partial protective effect that may be related to changes in the formation of lipid mediators derived from EPA and AA in retinal phospholipids.