Sepsis is defined as the systemic inflammatory response to infection. Phospholipase A(2) (PLA(2)) plays an important role in inflammation processes by initiating the production of inflammatory mediators. The role of cytosolic PLA (cPLA(2)) has not yet been identified in inflammatory and infectious disease clinical settings. The aim of the present research was to determine whether cPLA(2) activity has a role during sepsis. Since neutrophil activation has been documented during sepsis, these cells were chosen as a model to evaluate the function of cPLA(2) in this clinical setting. cPLA(2 )was studied at 3 levels: activity, protein expression, and messenger RNA (mRNA). Neutrophils from 32 septic patients with and without bacteremia were examined. cPLA(2) activity was measured using labeled phosphatidyl choline vesicles as a substrate, and total PLA(2) was determined by the release of labeled arachidonic acid from prelabeled cells. A significant increase in cPLA(2) activity, protein expression, and total PLA(2) activity in neutrophils was detected during sepsis. mRNA levels, detected by reverse transcriptase-polymerase chain reaction, were significantly higher during sepsis, indicating that the increase in the amount of cPLA(2) is regulated on the mRNA level. The significant elevation of cPLA(2) activity and expression in neutrophils during sepsis suggests that this enzyme plays a major role in neutrophil function in this clinical setting. (Blood. 2000;95:660-665)