Normal murine B lymphocytes are not known to be effectors of the Fc receptor‐mediated, antibody‐dependent cellular cytotoxicity (ADCC). In contrast, we report here that highly purified splenic B cells from mammary tumor‐bearing mice develop the potential of lysing antibody‐coated target cells. These lymphocytes are characterized by being G‐10 nonadherent, nylon wool adherent, sIg∗, FcR+, Thy 1.2−, asialo GM1−, and the immunoglobulin heavy‐chain genes of both chromosomes are rearranged. The lytic reaction is characterized by a noninterdigitating binding and by the appearance of endocytotic vesicles in the target cells. Nuclear disintegration occurs 18 h after initial effector‐target cell conjugate formation. At such time, only minor cytoplasmic membrane alterations are evident. The emergence of killer B cells in tumor‐bearing hosts indicates that all lymphoreticular cell types bearing Fc receptors are capable of mediating ADCC.— Lopez, D. M.; Blomberg, B. B.; Padmanabhan, R. R.; Bourguignon, L. Y. W. Nuclear disintegration of target cells by killer B lymphocytes from tumor‐bearing mice.FASEB J.3: 37‐43; 1989.