The aim of the study was to discover the mechanism of rejection of chondrocyte transplants introduced into articular cartilage defects. Chondrocytes from 3?5-day-old Lewis or WAG rats were liberated by enzymatic digesand tion from articular-epiphyseal cartilage complexes and implanted into defects made in the subpatellar region of the femur condyle of naive Lewis rats. Syngeneic transplants were also done after sensitization of the recipients with allogeneic chondrocytes injected intramuscularly. The transplants and synovial membrane were studied in periodate-lysineparaformaldehyde- fixed material with antibodies against B lymphocytes, CD4+ and CD8+ cells, NK cells, and macrophages. For detection of humoral response, chondrocyte lysates were subjected to protein electrophoresis and Western blotting with sera from the transplant recipients. Cartilage produced in intracartilaginous transplants of syngeneic chondrocytes did not show any signs of rejection. CD8+ lymphocytes and macrophages accumulated in the vicinity of cartilage produced by similar transplants in animals sensitized with intramuscular transplants of allogeneic WAG chondrocytes or bearing transplants of allogeneic WAG chondrocytes. CD8+ cells penetrated into the peripheral part of the cartilage, while macrophages advanced much more deeply. No specific anti-chondrocyte antibody was detected. The synovium from rats bearing intracartilaginous transplants of allogeneic chondrocytes or syngeneic chondrocytes after sensitization contained macrophages and CD8+ cells. The rejection of cartilage formed by syngeneic chondrocyte transplants in sensitized animals argues in favor of a chondrocyte-specific antigen expression. The involvement of the synovial membrane during transplant rejection suggests that it should be included in observations of the behavior of chondrocyte transplants introduced into articular cartilage.