A physiologically based kinetic model was used to predict the accumulation of a homologous series of chlorinated ethanes in fathead minnows (Pimephales promelas). Uptake and accumulation of these compounds are described in terms of a few fundamental physiological, morphological, and physicochemical parameters. Chemical residues in 30-d-old fathead minnows exposed to 1,1,2,2-tetrachloroethane, pentachloroethane, and hexachloroethane were used to evaluate model performance. The predicted and observed accumulations of the chlorinated ethanes were in close agreement. A quantitative assessment of the major factors regulating the exchange of these compounds indicates that the cutaneous surface may be an important route of uptake in small fish.