The oxygenated carotenoids zeaxanthin and lutein, found in the macular area of the retina, may offer protection against or repair of oxidative damage associated with the degenerative diseases of aging. Since both superoxide and nitrogen monoxide, which react to form peroxynitrite, are found in the retina, we studied the reaction of peroxynitrite with zeaxanthin in liposomes. Zeaxanthin was easily incorporated into liposomes constructed from the fully saturated lipid L-alpha-dimyristoyl-phosphatidylcholine (C14:0) and from egg lecithin, and its absorbance spectrum in liposomes strongly resembles in shape and amplitude that of zeaxanthin dissolved in methanol. The reaction between peroxynitrite and zeaxanthin is first-order in both substrates. The pH profile indicates that the reaction with zeaxanthin involves peroxynitrous acid and not the conjugate anion. We hypothesize that zeaxanthin plays a major role in protection of macular tissue from oxidative damage.