In summary, the source, absorption, metabolism, and disposition kinetics of several compounds that are potential markers of tobacco smoke consumption have been reviewed. Kinetic considerations have been applied to discuss specificity and sensitivity of various compounds as markers of cigarette smoking status, usefulness as quantitative indicators of tobacco smoke consumption, and optimal time for sample collection. One cannot, however, escape the conclusion that selection of a biochemical test must be linked to the hypothesis being tested. If only smoking versus nonsmoking is being assessed, then carbon monoxide and/or thiocyanate are inexpensive measurements that provide adequate information. If self-administration of nicotine or toxic effects potentially related to nicotine exposure are being studied, then measurements of nicotine exposure and consumption are required. Measurement of blood concentration of nicotine per se is necessary to document nicotine exposure; blood concentration of cotinine may be a better measure of daily nicotine consumption. To study potentially carcinogenic effects of tobacco smoke, specific measurements of carcinogen consumption must be developed and validated.