AbstractSmall particles of ultrahigh molecular weight polyethylene stimulate formation of foreign‐body granulomas and bone resorption. Bone formation may also be affected by wear debris. To determine if wear debris directly affects osteoblasts, we characterized a commercial preparation of ultrahigh molecular weight polyethylene (GUR4150) particles and examined their effect on MG63 osteoblast‐like cells. In aliquots of the culture medium containing ultrahigh molecular weight polyethylene, 79% of the particles were less than 1 μm in diameter, indicating that the cells were exposed to particles of less than 1 μm. MG63 cell response to the particles was measured by assaying cell number. [3H]thymidine incorporation, alkaline phosphatase specific activity, osteocalcin production, [35S]sulfate incorporation, and production of prostaglandin E2and transforming growth factor‐β. Cell number and [3H]thymidine incorporation were increased in a dose‐dependent manner. Alkaline phosphatase specific activity, a marker of cell differentiation for the cultures, was significantly decreased, but osteocalcin production was not affected. [35S]sulfate incorporation, a measure of extracellular matrix production, was reduced. Prostaglandin E2release was increased, but transforming growth factor‐β production was decreased in a dose‐dependent manner. This shows that ultrahigh molecular weight polyethylene particles affect MG63 proliferation, differentiation, extracellular matrix synthesis, and local factor production. These effects were direct and dose dependent. The findings suggest that ultrahigh molecular weight polyethylene wear debris particles with an average size of approximately 1 μm may inhibit bone formation by inhibiting cell differentiation and reducing transforming growth factor‐β production and matrix synthesis. In addition, increases in prostaglandin E2production may not only affect osteoblasts by an autocrine pathway but may also stimulate the proliferation and activation of cells in the monocytic lineage. These changes favor decreased bone formation and increased bone resorption as