Eight Chinese hamster clones (CHO-K1) growing at the 30 mg/ml concentration of 8-azaguanine (AG) were studied. Clones were differentiated by their resistance to AG and to 6-thioguanine, by their plating efficiency on HAT medium, and by the level of hypoxantine incorporation in cells. The differences in phenotypic properties were shown to be associated with variability in hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity. HPRT Michaelis constant (KM) for hypoxanthine and phosphoribosylpyrophosphate, and maximal reaction rate (Vm) offered considerable differences between all the resistant clones and sensitive cells. The only possible reason of these differences is a change in the HPRT coding locus. According to the results of the analysis of B15-4b-4 subclones, phenotypic and HPRT activity differences are also connected with each other; however, all subclones have the same KM of HPRT as that of the parental clone. So, differences in HPRT activity (and in Vm) may reflect changes in the HPRT content in cells of subclones. Hence, phenotypic heterogeneity of AG-resistant clones is determined by the interaction of mutational changes in the HPRT locus, and hereditable changes of genetic activity, responsible for variation of HPRT quantity in cells.