A series of MDR cell lines with various levels of P-glycoprotein have been established from a human colorectal carcinoma cell line, HCT-15, by stepwise exposure to adriamycin. The relative drug resistance of these cell lines correlated directly with both MDR1 mRNA levels and P-glycoprotein expression levels. Intracellular accumulation of adriamycin decreased inversely to their resistance. Drug sensitivities of these lines were reversed using verapamil. Since these cell lines are transplantable to nude mice, they may provide a useful animal model of MDR solid tumors for therapeutic experiments.