The fate of a second intra-articularly (i.a.) injected dose of bovine serum albumin (BSA) in an already established BSA-induced knee-joint inflammation was compared with that of a paired first arthritis-inducing injection of the same dose of BSA into the contralateral knee of immunized rabbits. External counting of i.a. radiolabelled BSA indicated more rapid initial elimination but approximately two-fold increase in long-term retention of BSA after a second i.a. injection as compared with a first one. Direct counting of dissected joint structures confirmed these data and localized the retained BSA predominantly in hyaline articular cartilage, menisci and ligaments, both after a first and after a second injection. Since the protocol used in these studies per se excluded systemic factors as possible determinants of the difference in antigen retention observed, local alterations in the already inflamed joint caused this difference. Control studies indicated that both humoral immune factors and non-specific inflammatory changes within the chronically inflamed joint determine the phenomenon. Local alterations in an immune-induced chronically-inflamed joint increase its antigen-binding capacity, a mechanism of possible relevance to the chronic course and the occurrence of exacerbations characteristic of some forms of human arthritis.