New adriamycin (ADR) resistant human leukemic cell lines (KY-ADR1 and KY-ADR2) have been established. KY-ADR1 was selected from a cytosine arabinoside (Ara C) resistant cell line by gradually increasing the concentration of ADR and KY-ADR2 from the parental cell line, KY-821, by the same method. The IC50s of both cell lines were 4.3 x 10(-5) and 3.6 x 10(-5) M ADR, respectively. Both lines revealed a similar cross resistance to various anticancer drugs, but KY-ADR1 was resistant to Ara C, whereas KY-ADR2 was sensitive. MDR1 gene was over-expressed and P-glycoprotein was expressed on the cytoplasmic membrane in both lines. Neither verapamil nor cyclosporin A could completely reverse ADR resistance. In addition, no significant changes in topoisomerase II and glutathione-s-transferase levels were detected. These findings indicate that ADR resistance in both cell lines is mainly mediated by P-glycoprotein and some other mechanism may be present. Interestingly, growth of both cell lines was stimulated by natural IL-1 and not affected by TNF alpha and IFN gamma, whereas growth of parental KY-821 was inhibited by these factors. These cell lines will provide new biological aspects on drug resistant leukemic cells.