BACKGROUND According to epidemiological and experimental studies, inhalation of nanoparticles is commonly believed as a main trigger for several pulmonary dysfunctions and lung diseases. Concerning the transport and deposition of such nano-scale particles in the different structures of the human lungs, some essential questions are still in need of a clarification. Therefore, main objective of the study was the simulation of nanoparticle deposition in the alveolar region of the human respiratory tract (HRT). METHODS Respective factors describing the aerodynamic behavior of spherical and non-spherical particles in the inhaled air stream (i.e., Cunningham slip correction factors, dynamic shape factors, equivalent-volume diameters, aerodynamic diameters) were computed. Alveolar deposition of diverse nanomaterials according to several known mechanisms, among which Brownian diffusion and sedimentation play a superior role, was approximated by the use of empirical and analytical formulae. Deposition calculations were conducted with a currently developed program, termed NANODEP, which allows the variation of numerous input parameters with regard to particle geometry, lung morphometry, and aerosol inhalation. RESULTS Generally, alveolar deposition of nanoparticles concerned for this study varies between 0.1% and 12.4% during sitting breathing and between 2.0% and 20.1% during heavy-exercise breathing. Prolate particles (e.g., nanotubes) exhibit a significant increase in deposition, when their aspect ratio is enhanced. In contrast, deposition of oblate particles (e.g., nanoplatelets) is remarkably declined with any reduction of the aspect ratio. CONCLUSIONS The study clearly demonstrates that alveolar deposition of nanoparticles represents a topic certainly being of superior interest for physicists and respiratory physicians in future.