Detailed information on the composition-resolved size distribution of particulate matter deposited along the human respiratory tract can help linking epidemiological, toxicological, and pathological studies and thus potentially improve the understanding of the origin of pulmonary disorders induced by respirable pathogens. For this purpose, a new mechanistic dosimetry model describing the dynamics of respirable particles in the human airways was developed. Model predictions of transport and fate of inhaled aerosols are based on solutions of the aerosol general dynamic equation, which describes changes in particle size and mass distributions resulting from processes such as nucleation, condensation, coagulation, gas phase chemical reaction, and deposition. To compensate for approximating the three-dimensional problem by considering only axial variations along the airways, boundary layer effects are introduced via appropriate dimensionless transport parameters. The architecture of the human lung is described by Weibel's simple regular dichotomous model. An important advantage of the present approach is that it allows testing the significance of intersubject lung morphology and ventilation variability for particle deposition and dose calculations. The model predicts the evolution of size and composition distributions of inhaled particles and the deposition profile along the human lower respiratory tract: in general, model predictions are in qualitative and quantitative agreement with tracheobronchial and alveolar deposition data.