Phenolic organochalcogen chain-breaking antioxidants, i.e. 6-bromo-8 (hexadecyltellanyl)-3,3-dimethyl-1,5-dihydro-[1,3]dioxepino[5,6-c]pyridin-9-ol and 2-methyl-2,3-dihydrobenzo[b]selenophene-5-ol, have been investigated in a two-phase (chlorobenzene/water) lipid peroxidation model system as potent inhibitors of lipid peroxyl radicals with various co-antioxidants at various pH values. The pH has a significant effect on the chain-breaking antioxidant activities of phenolic organochalcogens. The key chain-breaking mechanism profile was attributed to the first oxygen atom transfer from the lipid peroxyl radicals to the Se/Te atom, followed by hydrogen atom transfer in a solvent cage from the nearby phenolic group to the resulting alkoxyl radical. Finally, regeneration of organochalcogen antioxidants could take place in the presence of aqueous-soluble co-antioxidants. Also, in the presence of aqueous soluble N-acetylcysteine at pH 1-7, both antioxidants behaved as very good inhibitors of lipid peroxyl radicals. The role of aqueous soluble mild co-antioxidants in the regeneration studies of organochalcogen antioxidants has been investigated in a two-phase lipid peroxidation model system. The importance of the phase transfer catalyst has been explored in the inhibition studies of selenium containing antioxidants using an Fe(II) source. The overall pH-dependent antioxidant activities of organochalcogens depend on their hydrogen atom transfer ability, relative stability, and distribution in the aqueous/lipid phase.