10 independent clones of Djungarian hamster DM-15 and DMCAP cells 16-22-fold resistant to colchicine were obtained. The drug resistance was unstable. During cultivation in a colchicine free medium, 1-2% cells per population doubling lost resistance to selective dosage of the drug (0,1 microgram/ml). The loss of colchicine resistance was stepwise: the cells lost resistance to some concentrations of the drug but retained resistance to the lower colchicine dosages toxic for the wild-type cells. The analysis of chromosomes stained by the trypsin G-banding technique showed the specific karyotypic alteration in all the cells of 10 clones, i.e. complete or partial trisomy of chromosome 4. In addition, in some cells of 7 clones small chromatin bodies (SCB) and chromosomes bearing long homogeneously staining regions (HSRs) were found. The loss of colchicine resistance was accompanied by the disappearance of cells containing SCB and HSRs and the decrease in the number of cells with trisomy 4. However, the direct correlation between the loss of drug resistance and that of additional material of chromosome 4 was not observed. Probably, the resistance to colchicine is connected in these clones with gene amplification, and trisomy 4 is involved in the development of gene amplification.