We investigated the in-vivo proteoglycan synthesis in specific areas of murine knee joint articular cartilage after the induction of degenerative joint disease by means of 35S-sulphate autoradiography. Degenerative joint disease was induced either by direct interference with cartilage metabolism (papain and iodoacetate), or by the induction of joint instability (collagenase). Injection of iodoacetate and papain led to inhibition of proteoglycan synthesis mainly in the central parts of the patellae, patellaris femoris and the central part of the medial tibial plateau. Articular cartilage adjacent to the strongly inhibited areas frequently showed a significantly enhanced synthesis of proteoglycans. A strong inhibition of proteoglycan synthesis was observed in the central part of the medial plateau after collagenase injection while other cartilage sites and joint structures such as the capsule and ligaments were stimulated in their proteoglycan synthesis. This study shows that the localization of changes in cartilage metabolism in degenerative joint disease of the knee might be related to differences in the pathogenetic mechanism in different variants of this common joint disorder.