Protein binding has been recognized as an important consideration in pharmacokinetic modeling of drugs since the early 1980s (Kruger-Thiemer et al., 1966). As toxicokinetic models are increasingly applied in the assessment of xenobiotic uptake, distribution and elimination in aquatic species, the paucity of relevant data for plasma protein binding becomes apparent. The present project was an attempt to empirically dissimilar chemicals to rainbow trout and rat plasma proteins. The study attempts to relate plasma protein binding and chemical lipophilicity, as represented by log octanol water partition coefficients (Log P). The in vitro binding of I-butanol, phenol, nitrobenzene, and pentachlorophenol in trout plasma and rat plasma was determined. Binding to rainbow trout plasma proteins agreed within 9% of that observed in rat plasma. Percentage bound to rainbow trout (C-99%) or rat (10-99%) plasma proteins increased as the log octanol water partition of the chemicals increased within the Log P 1-3 range, and was suggestive of hydrophobic interactions in binding.