Summary Natural anti-chondrocyte cylotoxicity of normal rat splenocytes, peritoneal cells and thymocytes was tested by means of ^'Cr-release assay. Chondrocytes derived from epiphyseal, costal, nasal, and auricular cartilages were used as target cells. In some experiments, erythroleukaemic K-562 cells, known as typical natural killer cell targets, were also used. All types of chondrocytes were lysed equally well by splenocytes. Peritoneal cells exerted a low cytotoxic effect, whilst very low. almost negligible, cytotoxicity was noted with thymocytes. Negative selection with antibodies and complement showed that spleen-derived anti-chondrocyte effector cells arc endowed with surface ganglioside asialo-GMI. A similar result was obtained in parallel experiments with K-562 cells. Moreover, 'cold' target experiments demonstrated that the release of ^'Cr from the labelled chondrocytes could be inhibited by addition of untabclled chondrocytes and K-562 cells.