Self‐replicating, self‐calcifying nanosized particles (NPs) can be isolated from mammalian blood and calcified human tissue. Intravenous injection of these biologic NPs into rabbits accelerates occlusion of endothelium‐denuded carotid arteries. Since platelet activation is an initiating step in arterial repair, experiments were designed to determine if biologic NPs alter platelet functions. Platelet rich plasma was prepared from human citrate anti‐coagulated blood. Platelet aggregation (light transmission) and ATP secretion were monitored in response to sTRAP (10 μM) prior to and following incubation with either control solution, biologic NPs (50, 150, 500 NTUs) or hydroxyapatite (HA). NPs increased light transmission and ATP secretion when added immediately to the platelet solution. Both rate and maximal aggregation induced by sTRAP were reduced in the presence of NPs. NPs increased stimulated release of ATP at moderate doses but only after 15 minutes of incubation. HA crystals reduced rather than augmented ATP secretion. These results suggest that NPs cause a shape change in platelets and formation of microaggregates under basal conditions. NPs selectively augment agonist‐stimulated ATP secretion in a dose and time dependent fashion. Therefore, NP activation of platelets could contribute to the increased vascular response to injury in vivo.