Phospholipase A₂, lysolecithinase, and lysolecithin-lysolecithin acyltransferase are present in the airway secretions of patients with asthma, cystic fibrosis (CF), and alveolar proteinosis. Assays of these enzymes under the same conditions in extracts of human polymorphonuclear leukocytes, alveolar macrophages, and pig tracheal mucosa indicated that these extracellular airway enzymes were probably not derived from these cell types. Although the above three enzymes were present in secretions of all patients with these three diseases, large amounts of palmitoyl lysolecithin, free fatty acids, and dipalmitoyl lecithin were found only in patients having alveolar proteinosis and asthma. The amount of free fatty acids in these secretions was sufficient to inhibit both the lysolecithinase and the lysolecithin-lysolecithin acyltransferase, but not the phospholipase A₂. These findings suggest that the large amount of dipalmitoyl lecithin, free fatty acids, and lysolecithin found in these secretions results from extracellular remodelling by these enzymes. Because the phospholipase A₂ was present in large amounts, it was possible after delipidation to purify it to homogeneity. It is a stable enzyme with an apparent molecular weight of 75,000 as estimated by SDS-mercaptoethanol gel electrophoresis.