For the purpose of risk evaluation, passive smoking is frequently regarded as low-dose cigarette smoking. However, since the physical, chemical and biological properties of mainstream smoke (MS), which is inhaled by the smoker and environmental tobacco smoke (ETS), which is breathed by the passive smoker are quite different, risk extrapolation from active smoking to passive smoking is of doubtful value. In a series of experimental exposure studies we compared the uptake of tobacco smoke constituents by active and passive smoking. The results show that biomarkers which were found to be elevated after experimental ETS exposure, such as nicotine and cotinine in plasma and urine as well as thioethers in urine, indicate gas-phase exposure in passive smokers, but particle-phase exposure in active smokers. Biomarkers which should indicate the uptake of particle-bound, genotoxic substances with ETS, such as urinary mutagenicity, metabolites of polycyclic aromatic hydrocarbons (PAH) and DNA adducts, were not found to be elevated even after extremely high ETS exposure. From these results we conclude that a risk evaluation for passive smoking on the basis of dosimetric data is currently not possible.