Recently, it was demonstrated, using nonpolar and polar narcotics, that volume fraction analyses can be used as a tool for distinguishing different mechanisms of action. The present study expanded upon this thesis by evaluating chemicals thought to act through the weak acid respiratory uncoupler and primary amine narcosis mechanisms. Toxicity data used in these evaluations were the 96-hour flow through SO percent mortality for the fathead minnow Pimephales promelas and the 48-hour static 50 percent inhibitory growth concentration data for axenic cultures of the ciliate Tetrahymena pyriformis. The target/water partition coefficients (Ktw) were analyzed and assumed to be a power function of Kow (Ktw = Kow(1-a)) where “a” describes hydrophobicity of the target site and assumed to be constant for a given mechanism of action. The “a” values and the mean volume fraction (MVF) for fish and ciliates, were determined for each mechanism of action. The results suggests volume fraction analyses can be used to distinguish different mechanisms of action by meeting one of the following criteria: 1) if “a” values are different, MVF values do not matter; 2) if “a” values are the same, MVF values must be different.