Determination of the exposure of adult smokers to cigarette smoke is of significance to the public health community, and integral to the development of reduced harm cigarette products. To evaluate future reduced harm products, a baseline study has been designed to determine actual exposure of U.S. adult smokers to cigarettes currently available in the U.S. market. The study population will include adult smokers of all major U.S. brands and include all 'tar'/nicotine yield categories. Smoke constituents and relevant biomarkers of exposure and effect to be determined in this study have been identified. A pilot study has been incorporated in the experimental design and results from the pilot will be used to estimate sample size for the baseline study. A questionnaire has been constructed to characterize smoking behavior and identify sources of confounding for biomarkers, both dietary and environmental. A statistical plan for data assessment and evaluation has also been devised. Details of this experimental design will be presented.