Leukotrienes are involved in diseases associated with a neutrophilic infiltrate. The role of human keratinocytes in the metabolism and inactivation of leukotrienes has not been thoroughly examined. We added exogenous radioactive leukotrienes to cultured human keratinocytes and evaluated the metabolic products using high-performance liquid chromatography. Over a 24-h period, unstimulated cultured keratinocytes convert leukotriene B4 to unidentified polar molecules. Leukotriene C4 is converted to a leukotriene D4/leukotriene E4-like product. Cultured human keratinocytes have the ability to metabolize leukotrienes and thus the keratinocyte may play a major role in the in vivo metabolism of leukotrienes produced during inflammatory dermatoses.