A detailed analysis was made of the karyotype of human hepatocarcinoma cell line PLC-PRF-5 containing an integrated hepatitis B viral genome and 10 mutant clones derived from the line. These clones are drug resistant and display features of cell differentiation. Cytogenetic manifestations of gene amplification common to many cells resistant to drugs were not observed in these clones, but certain tendencies of karyotype evolution involving material from chromosomes 7 and 11, as well as chromosomes 5 and 15, were recorded for a group of cytostatic-resistant clones. An increase in polyploid cell number and number of cells with chromosome pulverization as compared with the original line was noted in the clones. This phenomenon may be related to the cytopathic effect of the hepatitis B viral proteins, which have a higher expression in the clones.