In invertebrates, cytotoxicity can be an efficient natural defence system. Lysins can be secreted in the body fluids or act at the membrane level of the effector cells. Hemocytes appear to be responsible for the cytotoxic response to foreign, broad, or specific stimuli. The mechanisms by which lysins are released and function are not yet very well characterized. The findings about cell mediated contact dependent cytotoxicity suggest that multiple mechanisms must be considered. In allo‐ and xenogeneic reactions the specificity of cytotoxic mechanisms have been shown, In tunicates, humoral lysins have not been observed. Cytotoxic hemocytes, responsible for allo‐ and xenogeneic reactions, appear to be involved in graft rejections. Some properties of tunicate hemocyte cytotoxicity have been examined inCiona intestinalisusing erythrocyte targets. The reaction is fast, calcium‐dependent, behaves sigmoidally according to temperature, reaches a maximum at 37° C, and depends on membrane contact. Individual variability in lytic capacity ofCionaspecimens suggests that, as in the other invertebrate species, not all the hemocytes are cytotoxic. Sphingomyelin capacity to inhibit the reaction shows functional analogies with the pore‐forming hemolysins of echinoderm and polychaete species. However, it is not excluded that a hemocyte phospholipase may provoke the lysis of the target cell membrane. Thus the hypothesis is supported that a NK‐like activity appears early in the evolution thus contributing to the maintenance of homeostasis, and developing immunity.