Pulmonary dosimetry models are necessary for providing information on the regional effects of inhaled particles and gases in the respiratory tracts of humans and experimental animals. This information is important from a clinical standpoint for studying mechanisms of toxicant-induced lung disease processes and for considering the effects of chemicals on potentially sensitive human subpopulations. Experimental data can also provide fundamental information regarding normal physiological processes and facilitate the selection for the appropriate choice of animal models. Since differences exist in the way species respond to inhaled materials, a variety of factors, including anatomy, biochemistry, physiology, cell biology, andpathology, must be considered before extrapolating results from laboratory animals to humans. Moreover, reactions to toxicants are dependent on factors at the organ, tissue, cellular, and molecular levels; for example, metabolic differences among species clearly influence the transformation and/or clearance of inhaled materials. Anatomic variations in airway branching patterns and distal lung arrangements are major determinants of the distribution of inhaled toxicants and the sites of lung injury. In this respect, a thorough knowledge of species-specific morphological and functional characteristics is essential in order to fully comprehend structure-function relationships within species. A fundamental comprehension of similarities and differences among species is critical for making reasonable risk estimates regarding the toxicity of chemicals to humans. This review summarizes some of the existing data regarding species similarities and differences in lung responses to inhaled particles and gases. General concepts and mechanisms are emphasized at the beginning of each section, followed by relevant species comparisons of the following topics: