The relative toxicity of selected industrial organic chemicals was secured from the literature for the static 48-hTetrahymena pyriformis50% population growth impairment and the flow-through 96-hPimephales promelas50% mortality endpoints. Chemicals were selected to represent the nonpolar narcosis (aliphatic alcohols and aliphatic ketones) and polar narcosis (anilines and phenols) mechanisms of toxic action. molar volume (MV) and 1-octanol/water partition coefficient (logKow) data were generated for each chemical. High-quality, logKowdependent quantitative structure-activity relationships were observed for each chemical class and mechanism of action for both endpoints. The volume fraction (Vt) for each chemical in the target phase was determined from the toxicant concentration in the water (toxicity data), the MV, and the target/water partition coefficient (Ktw) withKtwconsidered equal toKow(1-a). Analyses of target sites, by way of “a” revealed that “a” was constant for a mechanism of action regardless of chemical class, but distinct for a given test system. MeanVtwas constant for each mechanism of action regardless of chemical class or test system. These results suggest, at least for reversible physical mechanisms, that volume fraction analyses are significant in determining the mechanism of toxic action of a chemical.