Summary of Work: The activity of cytosolic phospholipase A2 may be altered by calcium or by phosphorylation of serines in the cPLA2 molecule. A dual hybridization system in yeast was used to identify protein-protein interactions that might also be involved in the modulation of cPLA2 activity. Using this system, a member of the 5-100 family of proteins was identified as interacting with cPLA2. In in-vitro assays, this protein, p11, was found to inhibit phospholipase A2 activity. Immunoprecipitation of epithelial cell lysates using anti- cPLA2 antibody co-precipitated p11 protein. Antisense inhibition of production of this protein increased arachidonic acid release from airway epithelial cells. Therefore, p11 appears to be capable of modulating cPLA2 activity.