Group IIA phospholipase A2 (PLA2-IIA) is a newly recognized antibacterial acute phase protein. The concentration of PLA2-IIA increases up to 500-fold in the blood plasma of patients with severe acute diseases, compared with healthy persons. Despite numerous studies, the exact roles of this enzyme in human diseases are unknown. This study investigated the antibacterial properties of PLA2-IIA in human acute phase serum. PLA2-IIA in serum samples of patients with bacterial infections was capable of killing 90% of Staphylococcus aureus and 99% of Listeria monocytogenes in vitro after incubation for 2 h. At concentrations found in normal human serum, PLA2-IIA killed 90% of L. monocytogenes but did not kill S. aureus or Escherichia coli. The bactericidal effects of acute phase and normal human serum were abolished after depletion of PLA2-IIA by immunoadsorption.