Fragments of human epidermis were incubated in the presence of exogenous arachidonic acid. The incubates were subjected to reversed-phase and straight-phase high-performance liquid chromatography and finally the identity of the arachidonic acid metabolites of the 12-lipoxygenase pathway was determined by means of gas chromatography/mass spectrometry. It was found that human epidermis produces 8-hydroxy-11,12-epoxy- and 10-hydroxy-11,12-epoxyeicosatrienoic acid, 8,9,12-, 8,11,12- and 10,11,12-trihydroxyeicosatrienoic acid, 12-keto-eicosatetraenoic acid and 12-hydroxy-eicosatetraenoic acid derived from arachidonic acid via the 12-lipoxygenase pathway. As far as is known, this is the first time that a systematic and complete characterization of arachidonic acid metabolism through the 12-lipoxygenase pathway in human epidermis has been reported. Some of the eicosanoids characterized have potent biological activities that suggest their role in the inflammatory response on human skin.