In light of the exponentially increasing industrial production and consumer use of ultrafine particles, deposition in the human lung is of great environmental and biomedical concern, especially for children, asthmatics and the elderly. Considering spherical nanoparticles in the 1-100 nm mean-diameter range and different breathing routes with Q(total) = 30 and 60 L/min, local deposition fractions and global surface concentrations were predicted employing an experimentally validated computer simulation model. It was found that the change in breathing route (from nasal to oral breathing) not only significantly influences nanoparticle deposition in the regions of nasal and oral cavities, nasopharynx and oropharynx, but also measurably affects depositions from pharynx to bronchial airways for tiny nanoparticles (<= 5 nm). The effect of breathing routes on deposition of larger nanoparticles (> 5 nm) after the pharynx tends to be minor. The impact of different outlet flow-rate ratios generated by downstream resistances, e.g., caused by airway inflammation or tumors, is discussed in this study as well. Specifically, different outlet pressures primarily influence the velocity profiles and nanoparticle deposition fractions at that particular branch and adjacent bifurcations. In addition, the impact of change in outlet flow rate ratio on total deposition is confined to all same-level bifurcations and direct upstream-level bifurcations. The mass transfer coefficients of depositing nanoparticles (in terms of Sherwood number) can be well correlated as a function of Reynolds number and Schmidt number. The influence of downstream resistance on the Sherwood number in bronchial airways is smaller than intra-subject effects, i.e., variations of bifurcation levels and geometric parameters. (C) 2011 Elsevier Ltd. All rights reserved.