The inactivate streptococcal preparation OK432 activates the cytotoxic function of natural killer (NK) cells. Moreover, it induces cytotoxic activity against freshly isolated tumor cells. The present study was aimed at assessing whether OK432-activated effector cells expressed cytotoxicity against tumor cells pleiotropically resistant to cancer chemotherapy agents. OK432-treated lymphoid cells killed the multidrug resistant (MDR) LOVO DX line as efficiently as drug sensitive parental LOVO N carcinoma line. Effector cells involved in killing MDR cells were low density large granular lymphocytes with NK functions. Activation of effector cells has the potential to complement conventional cytoreductive therapy by eliminating residual-tumor cells surviving and resistant to chemotherapy.