Cartilaginous wear particles were retrieved from synovial fluid aspirates of human diarthrodial joints and added to cultures of human or murine mononuclear phagocytes or human synovial cells. In each case, addition of the wear particles elevated the production of proteinases active at neutral pH against collage, gelatin, azocasein and the synthetic pentapeptide phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg. Synovial cells secreted more than five times as much collagenase as the same number of the other cells. All types of cell secreted significant quantities of enzymes active against the noncollagenous substrates. Mild treatment of the spent media with trypsin stimulated all of these eurmymic activities. The spent culture media of synovial cells which had been exposed to cartilaginous wear particles released hydroxyproline and glycosaminoglycan from powdered cartilage, indicating the production of enzymes which degrade both the collagen and proteoglycan of th cartilaginous matrix. Cultures of mononuclear phagocytes, in contrast, while solubilizing chondroitin sulphate from cartilage, released very little hydroxyproline. The ability of wear particles to elicit these effects suggests a role for them in the pathogenesis of osteoarthritis and other types of joint deterioration.