Several ClchR clones of CHO-K1 have been isolated by a single- and multistep selection. They are distinct from each other both in the level of colchicine resistance and in the phenotypic stability of this feature. Fluctuation tests showed that the generation of drug resistant variants in the wild type population was random and did not depend on the action of selective agent. The rate of spontaneous occurrence of these variants was approximatley 1.79 x 10(-6) per cell per generation. Treatment with MNNG enhanced the frequency of ClchR variants by 100 fold. Cytotoxic effect of Clch on resistant cells has been potentiated by non-ionic detergent Tween 80. All the stable resistant clones appeared to be cross resistant to unrelated drugs such as actinomycin D, ethydium bromide and aminopterine . These two observations allow to suggest the alteration of membrane permeability as a mechanism of resistance to Clch . Genetical mechanisms of Clch -resistance of cells are discussed.