Cathepsin B and L activity was studied histochemically in arthritic rat ankle joints using specific synthetic substrates in a post coupling method on unfixed and undecalcified cryostat sections of rat ankle joints. Activity was strongly increased in chondrocytes and cells of the inflamed synovium with the development of arthritis induced by the synthetic adjuvant CP20961. Activity reached a maximum 20 days after induction of arthritis and decreased as the rats entered natural remission. Cathepsin B and L were at their highest level when macrophages were present in the joint space, as shown by using monoclonal antibody markers for rat macrophages (ED1 and ED2) in a biotin-avidin immunoperoxidase assay. This suggests that the macrophage infiltrate may have stimulated proteinase production in chondrocytes through cytokine release. The profile of appearance of cysteine proteinases suggests their involvement in the breakdown of cartilage and bone in the arthritic joint.