Multidrug Resistant (MDR) plays a major role in chemoresistance. Alpha Interferon (IFN) and all trans retinoic acid (ATRA) have antiproliferative effect and IFN regulates several genes, some of them implicated in the regulation of MDR gene expression. We have studied the modulations of adriamycin cytotoxicity by IFN and/or ATRA on K 562 (MDR-) and resistant to adriamycin K 562 adri (MDR+) cell lines. We observed an important increase of adriamycin cytotoxicity on both K 562 and K 562 adri by low dose of IFN and ATRA. Studies of MDR gene expression shows an increase in K 562 adri after exposure to IFN or ATRA. So the observed effect is not due to a down regulation of MDR gene expression but probably to the own antiproliferative effect of IFN and ATRA in combination with the cytotoxicity of adriamycin.