Fish physiologists have provided the basic information on gill morphology, gill function, and vascular dynamics with which to understand branchial flux of gases, water, and ions. In addition, pharmacologists and toxicologists, working in the area of drug action, have characterized the physicochemical attributes of xenobiotic chemicals that determine their rate of movement across biological membranes. Recently, aquatic toxicologists have applied the information to the question of what mechanisms control the movement of organic chemicals across fish gills and how exchange is affected by chemical properties. Mathematical models were developed that predict gill exchange as a function of basic processes such as water flow across the gills, blood flow through the gills, partitioning of the chemical between water and blood, and diffusion between blood and water across gill epithelia. Such mechanistic models can predict the effects of environmental conditions on exchange rates of xenobiotics. To fully develop a predictive capability for xenobiotic uptake and distribution by fish, it will be necessary to incorporate these gill models into emerging, physiologically based models for the entire animal.