The objective of our research is to model physical and biological processes related to the development of adverse health effects, especially initiation of lung cancer in the central human airways following inhalation of aerosol particles. There is experimental evidence that bronchogenic carcinomas originate mainly at the dividing zone of large central airway bifurcations where primary hotspots of deposition have been found. However, current lung deposition models do not take into consideration the inhomogeneity of deposition within bronchial airways. The flow field within three-dimensional morphologically realistic geometries of airway generations 3–6 of the human tracheobronchial tree is computed by the FLUENT CFD (computational fluid dynamics) code for a wide range of flow rates during both inhalation and exhalation. A large number of particle trajectories has been simulated to determine the resulting deposition patterns, which were finally quantified by local deposition enhancement factors. Both the local airflow fields and deposition patterns strongly depend on the shape of the geometry, especially on the form of the carinal ridge. The computed enhancement factors indicate that local deposition densities may be two orders of magnitude higher than the average values for scanning on the surface by a 100 × 100 μm surface element, i.e. at approximately cellular dimensions.