Various organic solvents may be encountered in contaminated water supplies at U.S. Environmental Protection Agency-designated Superfund sites. Human exposure to these environmental contaminants may occur by oral, dermal, or inhalation routes. The estimation of human health risk associated with exposure to these solvents can be improved through the use of physiologically based pharmacokinetic (PBPK) models to describe the absorption, tissue distribution, metabolism, and elimination of the compounds following any route of exposure. However, development of these PBPK models requires information on the relative solubility, or partition coefficient, of each compound in blood and various tissues. A number of investigators have provided partition coefficient information on different tissues in various species; however, the data for route of entry organs (i.e., skin, lung, stomach) and brain tissue are not complete. Therefore, the objective of this work was to replicate partition coefficient studies for several commonly encountered environmental contaminants using an in vitro gas-phase vial equilibration technique and to include tissues to evaluate brain, lung, stomach, and skin. A comparison of the partition coefficient values determined here with values reported in the literature, where available, showed good agreement in nearly all cases. An additional study was conducted to compare the liver-to-air partition coefficient values for toluene, benzene, and o-xylene introduced as single chemicals to partition coefficient values determined with the chemicals introduced as a mixture of all three compounds. The similarities of the resulting values suggest that both labor and laboratory resources may be reduced when partition coefficients are determined as chemical mixtures.