To determine the effects of NSAIDs on cartilage and bone in osteoarthritis we have examined (a) the rates of drug uptake into cartilage; (b) the effects in vitro of the drugs on the synthesis and degradation of cartilage proteoglycans (PrGns), synovial production of interleukins (IL) 1, 6 and 8, and prostanoids; and (c) cartilage proteoglycan and synovial eicosanoid (Eics) concentrations, as well as bone histopathology and histomorphometry in subjects with primary osteoarthritis (OA) of the hip who received NSAIDs for approximately one year or longer prior to arthroplasty. While the latter study is still in progress results to date show that (a) the drug uptake may be a determinant of its actions, and (b) NSAIDs vary considerably in their effects on synovial production of IL's and Eics as well as cartilage PrGns. The summative effects of these parameters may influence the outcome of NSAIDs on cartilage and bone integrity.