A physiologically based model was used to predict the bioconcentration of a waterborne, neutral, non-metabolized xenobiotic compound in fathead minnows (Pimephales promelas) and Japanese medaka (Oryzias latipes). This study included a quantitative assessment of the primary mechanistic variables regulating uptake across branchial and cutaneous surfaces in these small fish. Model simulations suggest that branchial and cutaneous surfaces have approx. equal capacity to support exchange of 2,2',5,5'-tetrachlorobiphenyl (TCB). A large cutaneous surface-area-to-volume ratio and a relatively small diffusion distance across the skin in these fish both contribute to the relatively greater contribution of cutaneous absorption as compared to larger fish. The accuracy of model simulations was evaluated by comparison of predicted and observed bioconcentration of TCB in fathead minnows and Japanese medaka. The complete model, incorporating simultaneous branchial and cutaneous flux, predicts absorption of TCB that is in basic agreement with bioconcentration observed in this study. This suggests that the absorption of neutral waterborne xenobiotics by small fish (< 4 g) can be accurately described in terms of a few fundamental physiological, morphological and physico-chemical parameters and that a physiologically based modeling approach can be used effectively to predict the bioconcentration of xenobiotics in small fish.