Physiological and biochemical factors determine the kinetic patterns of uptake, distribution, metabolism, and elimination of inhaled gases and vapors. For metabolically inert gases, true equilibrium is achieved after appropriately long exposures and the overall shape of the time-course curves of uptake and elimination should be concentration-independent. At equilibrium, achieved internal concentrations will be linearly related to exposure concentration. The rate of approach to equilibrium depends on blood flows for poorly soluble chemicals and on alveolar ventilation for soluble gases and vapors. For metabolized gases and vapors, steady-state is achieved where net pulmonary uptake replaces chemical removed from the circulation by metabolism. The shape of time-course curves for soluble, well-metabolized chemicals will be concentration-dependent, and steady-state blood:gas concentration ratios will be complexly related to inhaled concentrations. Physiological models of inhalation pharmacokinetics allow extrapolation of results in one species to untested species, based on knowledge of changing physiology between animal-to-animal. Two potential applications of interspecies extrapolation are discussed.