Dipalmitoylphosphatidylcholine is a unique species of lecithin which functions as the major surface-active agent of the pulmonary alveolar surfactant complex. In lung it comprises a major fraction of total lecithin whereas in other tissues it is present in only minimal amounts. This must result from a high degree of specificity in particular key steps of its production. However, these steps remain to be identified and detailed. That is the aim of our studies. Our initial efforts were concentrated on CDP-choline:diglyceride cholinephosphotransferase, the enzyme responsible for the majority of de novo lecithin synthesis in the lung. It was found that the substrate specificity of this enzyme for the diglyceride acceptor was very borad and could not alone account for the relative abundance of dipalmitoylphosphatidylcholine in lung. Therefore, we have also turned our attention to enzyme activities whose combined actions could result in the restructuring of already synthesized lecithins. These activities include the phospholipase A2 and lysolecithin transacylase activities of lung. Evidence for at least two non-lysomal phospholipase A2 activities has been obtained. One is calcium dependent; the other calcium independent. The subcellular localization and substrate specificity of each are subjects of ongoing investigations in our laboratory. We have found that pulmonary lysolecithin transacylase activity displays two pH optima. Whether this reflects two separate enzyme species or an unusual behavior of only one species is also a current subject of study. Further, attempts at greater purification of the transacylase activity and characterization of its substrate specificity are currently being undertaken.