We studied the effects of repeated intra-articular injections of sterile 140 mM NaCl solution on articular cartilage in adult rabbits. After 20 injections into the knee joints over a period of 4 weeks, chondrocyte glucosaminoglycan synthesis was evenly reduced in all cartilage layers, accompanied by a significant proteoglycan depletion of the matrix which was most marked in the superficial half of the cartilage. These and other changes only partially reversed during a further 4-week period after the injections had been stopped. Our data underline the need for a clear-cut indication for intra-articular injections. The microtrauma caused by injection, in conjunction with the introduction of a carrier solution into the joint, may, at least when repeated at short intervals, lead to measurable damage to the articular cartilage.