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The histological and histochemical changes in the meniscus of the adult rabbit were investigated after eight weekly intra-articular injections of prednisolone acetate. Light microscopic changes included decreased intensity of staining with either safranin O or toluidine blue O, hypocellularity, fibrillation, and tearing of the meniscus. Transmission electron-microscopic examination demonstrated a marked decrease of intracytoplasmic organelles and immature collagen fibrils, separation and deformation of collagen fibers, and the loss of safranin O-positive stellate granules in the pericellular space and between collagen fibers. CLINICAL RELEVANCE: The results of this study, although it was done in rabbits, demonstrate the possible deleterious effects of repeated intra-articular injections of corticosteroid on the human meniscus.