In comparison to human cells, cell lines of Chinese hamster and mouse origin exhibit between 10-50-fold resistance to a number of different drugs (viz. actinomycin D, daunomycin, chromomycin A3, colchicine, maytansine, mithramycin, puromycin, rhodamine 123, vinblastine and taxol). Studies with a representative Chinese hamster line (CHO) and a single-step multidrug resistant (MDR) mutant of human (HeLa) cells show that: (i) In comparison to the sensitive human cells, both cell lines show a comparable degree of resistance to the above mentioned drugs; (ii) In the presence of non-toxic dosage of verapamil, the drug-resistance phenotype of both cell lines is completely reversed; (iii) Both these cell lines showed greatly reduced uptake/intracellular levels of 3H-daunomycin, 3H-puromycin and 3H-vinblastine, which was restored to sensitive human cell's level in the presence of non-toxic doses of verapamil. The striking similarity in the behaviour of the naturally resistant Chinese hamster cells and a human MDR cell line with regard to the above characteristics, strongly suggests that the species-related differences in sensitivity to the above drugs result from a similar mechanism as that responsible for the MDR phenotype.