The histology and ultrastructure of the tissue response to particles of acrylic bone cement have been studied in rat and guinea pig muscle. Initially the implant formed an avascular zone of extracellular particles which rapidly became infiltrated by neutrophils. The particle zone was then progressively incorporated into new tissue by an ingrowth of small blood vessels accompanied by macrophages, murtinucleate giant cells and some fibroblasts.' Acrylic particles were phagocytosed into macrophages and giant cells. The giant cells often had a characteristic ring form. After vascularization and incorporation was complete, the macrophage and giant cell accumulation acquired a basically stable histological appearance over study periods of up to 2 yrs. A large majority of these cells appeared viable, and no zones of tissue necrosis were seen. However, occasional individual shrunken necrotic cells of unidentified origin and occasional individual tiny foci of nuclear debris were sometimes observed, sparsely distributed amongst the response, and a minor degree of neutrophil reaction was noted amongst some, but by no means all, of the long-term implants. The interpretation of morphological assessment for tissue toxicity is discussed. No evidence was obtained for the induction of cell-mediated hypersensitivity or of neoplasia by the cement particle preparations used.