A variant clone resistant to high doses of colchicine (KB-C1) derived from human cancer KB cell line is resistant to various anticancer agents. The KB-C1 cells were much more resistant to epidermal growth factor and a chimeric toxin, EGF-Pseudomonas exotoxin (PE), than the parental KB cells. KB-C1 cells have decreased numbers of EGF-receptors, though the affinity of the receptors is similar to that in the parental KB cells. A drug-sensitive revertant (C1-R2) partially recovered its EGF-receptor activity. Northern blot analysis showed a decreased level of EGF-receptor mRNA in KB-C1 cells, while the multidrug-resistance gene, mdr-1, was expressed at very high levels in KB-C1 cells, but not in KB or C1-R2 cells. The drug-resistant cells were less tumorigenic than the parental cells when injected into nude mice. A decreased expression of EGF-receptor in these cells may be one of the pleiotropic properties of multidrug-resistant cells and may perhaps represent the basis for their reduced tumorigenicity.