With the recent discoveries of novel forms of phospholipases A2 (PLA2s),2 new schemes for the roles of various PLA2s in lipid metabolism must be considered. The type II 14-kDa PLA2 isolated from human synovial fluid or platelet has many of the biochemical characteristics of the homologous snake venom and mammalian pancreatic PLA2s. It appears to function both as a cell-associated enzyme and extracellularly, where its expression and/or release is regulated by a variety of mediators such as cytokines or growth factors. The mammalian 85-kDa PLA2 purified from monocytic cells or platelets has no sequence homology to the 14-kDa PLA2 and exhibits biochemically different characteristics. It translocates from cytosol to particulate cell fractions in the presence of submicromolar levels of Ca2+ and has a substrate preference for sn-2-arachidonoyl-containing phospholipids. The cellular function and relative importance of these two enzymes in lipid metabolism remain to be determined. In this review, the biochemistry, localization, function, and regulation of these two distinct mammalian Ca(2+)-dependent PLA2 are compared.