We report on the identification of novel epoxide products formed during the autoxidative transformation of 15 S-hydroxy- and 15 S-hydroperoxy-eicosatetra-5 Z,8 Z,11 Z,13 E-enoic acids (15 S-HETE and 15 S-HPETE). These epoxides account for about 20-30% of the polar compounds detected during the early stages of autoxidation. Their common structural features are retention of the original 15 S-hydroxy or 15 S-hydroperoxy moiety with epoxidation of the 11 Z or 13 E double bonds in the conjugated diene of the starting material. Four main epoxyalcohol isomers were characterized from the hydroxy fatty acid 15 S-HETE, comprising two pairs of diastereomers with either an 11,12- trans or 13,14- trans epoxide functionality. Four main epoxyhydroperoxides identified from 15 S-HPETE comprised two pairs with cis or trans epoxide configuration at the 11,12 position. To account for these transformations, we propose a mechanism involving peroxyl radical dependent dimerization or oligomerization of the fatty acid hydroxy or hydroperoxy derivatives into covalent intermediates resulting in intermolecular transfer of oxygen from the peroxyl radical to the epoxide group. Autoxidation of [ (18)O 2]-15 S-HPETE carrying an O-18 labeled hydroperoxide showed that the 11,12- cis epoxy oxygen of the epoxy-hydroperoxide product was enriched in the labeled oxygen, providing evidence that in part it was derived directly from the starting hydroperoxide and not from molecular oxygen. Thus, intermediate dimerization and possibly oligomerization of fatty acid peroxyl radicals provides a mechanism of epoxidation of fatty acid derivatives during lipid peroxidation and a potential route to other products including aldehydes formed via carbon chain cleavage.