The distribution and disposition of a drug in the body result from a complex set of physiological processes and biochemical interactions. In principle it is possible to describe these processes and interactions in mathematical terms and, if sufficient data are available, to predict the time course of the drug and metabolite(s) in specific anatomical sites in the body. Allometric considerations have been employed in the development and application of physiological pharmacokinetic models. In fact the remarkable similitude of mammalian species forms the basis of much research in physiology, pharmacology and toxicology. Similitude is not equivalent to sameness. In biology as in engineering, the model system is never identical to the prototype. But appropriate use of model systems can provide considerable insight into basic principles, and these principles can be used in conjunction with other knowledge for a variety of pharmacologic applications. Some of these ideas are illustrated by a discussion of allometry, physiological pharmacokinetics, and the use of in vitro systems to predict drug metabolism in experimental animals and human subjects.