A VP-16-resistant subline was established from THP-1 human monocytic leukemia cells by subculturing in stepwise increasing concentrations of the drug. The resistant cells (THP-1/E) were capable of sustaining continuous growth in 1.0 microgram/ml VP-16. The 50% inhibition dose (IC50) was 1.4 micrograms/ml or a 35-fold of the parent cells. A more than 18-fold IC50 was also obtained with teniposide (VM-26). However, no substantial cross-resistance was observed with 5 other antineoplastic drugs, IC50 values being limited below several times of THP-1.