The T-cell-cloning assay was established to determine the frequency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutant lymphocytes in the presence of the selective agent 6-thioguanine in peripheral blood from a human control population. We investigated 44 healthy adults (blood donors) and found a mean mutant frequency of 7.2 x 10(-6) (geometric mean 5.6 x 10(-6). An elevated mean mutant frequency occurred in smokers as compared to non-smokers. However, a statistically significant increase was only observed between female smokers and female non-smokers while there was only a slight difference in the male group. A significant difference in mutant frequency could be found between individuals younger than 35 years and those above 35. But the difference of the mutant frequency with age showed up only among smokers. No significant effect of the gender was observed. Mutant frequency was inversely related to the cloning efficiency.