Multiple organ failure (MOF) is the most common cause of death in the surgical intensive care unit. We studied the relation of MOF to changes in the concentration of group II phospholipase A2 (PLA2) in serum. Altogether, 215 surgical intensive care patients with multiple injuries, diffuse peritonitis, or sepsis and control patients, who were at a high risk for postoperative sepsis after various surgical interventions, were included in the present prospective study. The clinical performance of the MOF score and the concentrations of group II PLA2 and C-reactive protein (CRP) in serum were studied using receiver operating characteristic (ROC) curves. The group II PLA2 level was considerably above normal in all groups of patients during the first week of observation. There was a highly significant difference in group II PLA2 levels between patients with severe infections (peritonitis and sepsis) and the other patients studied (multiple injuries and elective surgery) (ROC 0.931,P< 0.0001). The concentration of group II PLA2 had a significant positive correlation to the CRP level and body temperature, which indicates that group II PLA2 is an acute phase reactant and that the determination of group II PLA2 is a useful measurement to diagnose severe infections. It was concluded that the concentration of group II PLA2 in serum effectively predicts lethal MOF in patients with multiple injuries after the second day (ROC 0.739,P< 0.01) and in patients with diffuse peritonitis after the fourth day (ROC 0.750,P< 0.02).