The effect of the total fraction of human defensins (HNP-1, HNP-2, and HNP-3) on the cytoplasmic Ca 2* content ([Ca2*]i) in the platelets of healthy donors was studied. At concentrations of 0.1-40 gg/ml and an incubation time of 10 mm defensins have no effect on [Ca~+]i in platelets labeled with Fura-2AM. However, at higher concentrations (100 ~tg/ml) they increased platelet [Ca2+]i . In addition, defensins (40 ~tg/ml) inhibited the Ca 2 § increase in platelets induced by thrombin, adenosine diphosphate, and the lipopolysaccharide of S. typhimurium endotoxin. The most pronounced inhibitory effect was observed in a suspension of thrombin-stimulated platelets. It is shown that the effect of human defensins on the functional activity of platelets is due to the alterations in the intracellular Ca 2 §