12/15-Lipoxygenase is a highly regulated lipid-peroxidating enzyme whose expression and arachidonic acid metabolites are implicated in several important inflammatory conditions including airway and glomerular inflammation as well as atherosclerosis. Tissue expression of the original 12/15-lipoxygenase is well characterized in reticulocytes, eosinophils, airway epithelial cells, and monocytes/macrophages and is likely in other cell systems and tissues under specific conditions. The physiologic role of this family of enzymes is dependent on the context in which it is expressed. In general, the arachidonic acid metabolites antagonize inflammatory responses and counteract the proinflammatory effects of the 5-lipoxygenase pathway. However, certain diHETEs are associaled with pro-inflammatory effects, specifically neutrophilic and eosiniphilic chemotaxis. The direct action of these enzymes on complex lipids and cellular membranes also links them to such significant process as reticulocyte maturation, LDL oxidation in atherosclerosis and pulmonary host defenses. The availability of new specific inhibitors and murine lines that lack expression of the homologous 12-lipoxygenase will allow confirmation of many of these effects with in vivo models of inflammation.