In 81 healthy individuals (51 smokers and 30 nonsmokers) biological indicators of internal exposure to electrophiles derived from tobacco smoke through metabolism were evaluated. Subgroups of smokers have been established in relation to the amount and type of tobacco smoked. Acetylator and hydroxylator phenotypes have been used as biomarkers of genetically determined susceptibility to cancer development. Urinary concentrations of thioethers (UT) and mutagenicity, with S9 mix for microsomal activation (MI‐S9), were higher in smokers in relation to the level of tobacco consumption, but not to the type of tobacco. The “Slow acetylators‐rapid oxidizers” category was not significant from the “rapid acetylators‐rapid oxidizers” for values of UT and MI‐S9. Data suggest that the biomarkers of exposure used in this study lack the necessary specificity to ascertain genetically determined susceptibility to cancer induced by tobacco smoking.