Significant differences in lower respiratory tract structure exist both within species and among species at each level of anatomy. Irregular dichotomous and trichotomous branching patterns of airways are present in human and nonhuman primate lungs. In contrast, the dog and common laboratory rodents exhibit a predominantly monopodial branching system. The effects of these various branching patterns on airflow distribution, gas uptake, and the deposition of particles have not been sufficiently studied to determine the extent to which branching patterns impart regional inhomogeneities or local variations in the deposition of inhaled material. To date, detailed morphometric data have not been used to examine aerosol particle deposition. We have been using three-dimensional reconstruction techniques to examine various aspects of lung structure. Studies vary from the reconstruction of individual cells to reconstructing conducting airway and alveolar duct branching systems. When using physical models for dosimetric calculations, realistic geometry is critical to be certain that the model appropriately captures the complexity of the branching system studied. There are various length pathways to reach the alveolar (gas exchange) region in all types of mammalian lungs. The average path length involves about 16 branches from the trachea to the terminal bronchioles (Weibel, 1963; Raabe et al., 1976; Yeh et al., 1979), but short path lengths may have as few as 8 or 10 branches. Analyses in mouse, rat, and baboon lungs demonstrate that the greater lung size in larger species is the result of an increase in both the number and size of ventilatory units, with the major contribution associated with the change in number of ventilatory units. Here, a ventilatory unit is defined to be the collection of alveoli and alveolar ducts distal to the bronchiolar- alveolar duct junction. The ratio of ventilatory unit diameter to alveolar diameter is constant over a range of lung sizes from those of mice to men. A ventilatory unit is typically about 17.5 alveolar diameters in size. This new knowledge about lung structure and geometry applies to a number of areas. Among these are (a) examining lobar and path-specific deposition patterns for pharmaceutical aerosol distributions, (b) selecting critical sites for potential lung injury, and (c) establishing respiratory tract structure based criteria for the optimum design of pharmaceutical aerosols.