We tested the effect of an antagonist of platelet-activating factor (PAF), BN 52021, on both acute light-induced and light plus lithium-induced rod outer segment (ROS) lesions. Rats were fed lithium carbonate (2.6 g/kg chow) for 3 weeks. Half of the lithium-treated rats received BN 52021 (25 mg/kg) via gastric intubation prior to light exposure. Control and treated rats were exposed to 400-450 lux (measured at the eye level of the rats) of diffuse, white fluorescent light for 30 min, followed by 2 h of darkness and then decapitated. The eyes were removed and prepared for light and electron microscopic observation. The structural alterations of ROS were quantified from electron micrographs using a multifunctional computer image-analysis system. Our data show a significant reduction of ROS lesions by BN 52021, and this is most pronounced in light plus lithium-treated rats. Furthermore, in confirmation of previous studies, chronic lithium treatment significantly augmented light-elicited phagosome numbers, and BN 52021 reduced this effect. Our findings thus suggest that light and lithium may act via PAF responses in the rat retina.