The ability of lymphoid cells from normal mice to exert a natural cytotoxic activity against isolated syngeneic and allogeneic epiphyseal chondrocytes was studied by means of 51Cr release assay. We found, that both spleen and peritoneal cells, but not thymocytes, exerted an anti-chondrocyte cytotoxic effect. Addition of unlabelled chondrocytes markedly reduced experimental 51Cr release and the inhibitory effect was proportional to the number of 'cold' cells added. This indicate, that chondrocyte lysis was due to specific effector-target interaction. As no cytotoxicity was observed against isolated fibroblasts, our results could not be explained by lysis of fibroblasts contaminating chondrocyte cultures.