Trihydroxytetraenes, a novel series of oxygenated derivatives formed from arachidonic acid in human leukocytes, were recently isolated [Serhan, C. N., Hamberg, M. & Samuelsson, B. (1984) Biochem. Biophys. Res. Commun. 118, 943-949]. The structure of the major compound was established--i.e., 5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid. The present study reports the structure of a second member of the trihydroxytetraene series of compounds--i.e., 5D,14,15L-trihydroxy-6,8,10,12-icosatetraenoic acid. When added to human neutrophils, 5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid stimulated superoxide anion generation and degranulation at submicromolar concentrations without provoking a substantial aggregation response. With respect to superoxide anion generation, 5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid proved to be as potent as leukotriene B4. In contrast, the compound was approximately 2 orders of magnitude less potent than either leukotriene B4 or fMet-Leu-Phe at provoking degranulation. The results indicate that interaction(s) between the 5- and 15-lipoxygenase pathways of human leukocytes leads to formation of a new series of oxygenated derivatives of arachidonic acid that may be involved in regulating specific cellular responses. The trivial names lipoxin A (5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid) and lipoxin B (5D,14,15L-trihydroxy-6,8,10,12-icosatetraenoic acid) are proposed for the new compounds.