To estimate exposures to smokers from cigarettes, smoking topography is typically measured and programmed into a smoking machine to mimic human smoking, and the resulting smoke emissions are tested for relative levels of harmful constituents. However, using only the summary puff data--with a fixed puff frequency, volume, and duration--may underestimate or overestimate actual exposure to smoke toxins. In this laboratory study, we used a topography-driven smoking machine that faithfully reproduces a human smoking session and individual human topography data (n = 24) collected during previous clinical research to investigate if replicating the true puff profile (TP) versus the mathematically derived smoothed puff profile (SM) resulted in differences in particle size distributions and selected toxic/carcinogenic organic compounds from mainstream smoke emissions. Particle size distributions were measured using an electrical low pressure impactor, the masses of the size-fractionated fine and ultrafine particles were determined gravimetrically, and the collected particulate was analyzed for selected particle-bound, semivolatile compounds. Volatile compounds were measured in real time using a proton transfer reaction-mass spectrometer. By and large, TP levels for the fine and ultrafine particulate masses as well as particle-bound organic compounds were slightly lower than the SM concentrations. The volatile compounds, by contrast, showed no clear trend. Differences in emissions due to the use of the TP and SM profiles are generally not large enough to warrant abandoning the procedures used to generate the simpler smoothed profile in favor of the true profile.