The effects of human neutrophil peptide defensin were studied on human platelet function. Defensin (0.1-40 micrograms/mL) did not promote platelet aggregation. Defensin decreased platelet aggregation responses to ADF, collagen or thrombin. Defensin significantly lessened ATP level, released during platelet aggregation, and malondialdehyde production, induced by thrombin and collagen. These data reveal that defensins involve in cell-cell interaction between platelets and neutrophils counteracting agonist-induced platelet activation.