Agonist-induced release of arachidonic acid from membrane phospholipids and its oxygenation by specific enzymes to generate bioactive eicosanoids represent an important series of events that is thought to play a pivotal role in both physiologic and pathologic responses. Research during the past year confirmed and extended our knowledge of lipoxygenase activation and assembly of the 5-lipoxygenase complex in leukocytes. Many of the key enzymes and proteins in the arachidonic acid signaling cascade were identified, and rational drug design is in progress to interact with these targets. The role of transcellular biosynthesis in leukotrienes, lipoxins, and other novel eicosanoids is emerging as an important theme in eicosanoid formation in multicellular events including thrombosis, inflammation, and atherosclerosis. Moreover, new bioactions were identified for both leukotrienes and lipoxins. Counterregulatory roles demonstrated for lipoxins suggest that these compounds may serve as endogenous chalones generated via lipoxygenase- and cell-cell interactions.