Nanoparticulate materials are produced by industrial processing or engineered for specific biomedical applications. In both cases, their contact with the human body may lead to adverse reactions. Most of the published papers so far have focused on the cytotoxic effects of nanoparticles (NPs). Instead, the present in vitro study investigates the effect of different types of NP on key components of the host response such as clot formation and the inflammatory cells. The different NPs were pre-conditioned with platelet-rich human plasma for 30 min and then incubated with the blood mononuclear cells for 20 hours. The potential of the different NPs to induce clot formation, platelet activation and monocyte/macrophage differentiation was assessed by morphological analysis, immunocytochemistry and biochemical assays. The data showed that nanoparticulate materials based on antimony, silver and nickel were capable of promoting the polymerization of fibrin and the aggregation and fragmentation of platelets, leading to a moderately activated monocyte phenotype. This process was more pronounced in the case of antimony-and silver-based NPs that share a similar size and round-shaped morphology. Conversely, NPs of cobalt, titanium and iron appeared to stimulate cells to acquire a macrophage phenotype able to secrete higher levels of tumour necrosis factor a, a pro-inflammatory cytokine. Therefore, the present study provides clear indications about the subtle and adverse effects that the invasion of these materials may produce in the cardiovascular system and in vital organs.