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In this study, we investigated the effects of ultrahigh molecular weight polyethylene (UHMWPE) particles on the osteogenic activity of primary murine bone marrow osteoprogenitors and MC3T3\u2010E1 preosteoblastic cells <jats:italic>in vitro<\/jats:italic>. Submicron\u2010sized UHMWPE particles generated from wear simulator tests were isolated from serum\u2010containing solution by density gradient centrifugation. The particles were coated onto the surface of culture wells at concentrations of 0.038, 0.075, 0.150, 0.300, and 0.600% v\/v in a layer of type I collagen matrix. Primary murine bone marrow cells and MC3T3\u2010E1 preosteoblasts were seeded onto the particle\u2010collagen matrix and induced to differentiate in osteogenic medium for 20 days. Exposure of both cell populations to UHMWPE particles resulted in a dose\u2010dependent decrease in mineralization, proliferation, alkaline phosphatase activity, and osteocalcin production when compared with control cells cultured on collagen matrix without particles. Complete suppression of osteogenesis was observed at particle concentrations \u22650.150% v\/v. This study demonstrated that UHMWPE particles inhibit the osteogenic activity of osteoprogenitor cells, which may result in reduced periprosthetic bone regeneration and repair. \u00a9 2008 Wiley Periodicals, Inc. 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