The ability of carotenoids to protect egg-yolk phosphatidylcholine (EYPC) lipids against oxidation by peroxyl radicals generated from azo-initiators was studied. In homogeneous organic solution, all the carotenoids tested ameliorated lipid peroxidation by AMVN, but none was as effective as alpha-tocopherol. Beta-ring carotenoids showed a correlation between protective effect and rate of carotenoid destruction. Beta,beta-Carotene and zeaxanthin, which react with peroxyl radicals at similar rates, gave a similar degree of protection in organic solution. The reactivity and protective ability of the 4,4'-diketocarotenoids, astaxanthin and canthaxanthin was less. Carotenoids incorporated into ordered membrane systems (EYPC liposomes) displayed different protective efficacies. Zeaxanthin and beta-cryptoxanthin were more effective than beta,beta-carotene against oxidation initiated in the aqueous and lipid phases. Astaxanthin and canthaxanthin afforded less protection to the liposomal lipids. Lycopene was destroyed most rapidly but was least effective as an antioxidant. Located in the hydrophobic inner core of the bilayer, the hydrocarbons lycopene and beta,beta-carotene would not be in a position to readily intercept free-radicals entering the membrane from the aqueous phase. Carotenoids with polar end groups span the bilayer with their end groups located near the hydrophobic-hydrophillic interface where free-radical attack from AAPH first occurs. Hydrogen abstraction from C-4 may be one of the mechanisms of carotenoid antioxidant activity in this system. The chemical reactivity of a carotenoid is not the only factor that determines its ability to protect membranes against oxidation. The position and orientation of the carotenoid in the bilayer is also of importance.