This study concerns the relationship between hydrophobicity and bio-accessibility of environmental pollutants among Tetrahymena pyriformis (protozoan), Daphnia magna (water flea) and the fish Poecilia reticulata. The toxicological data of 55 chemicals in terms of 50% effect concentration (EC₅₀) was selected toward these three biological objects along with their hydrophobic potential (octanol-water partition coefficients (log K_ow)). Overall, a significant correlation was recorded among all test systems, with the highest between Tetrahymena pyriformis and Poecilia reticulata (R = 0.93). The acute toxicity results revealed substantial difference in the sensitivity of the three test systems but at a certain level of hydrophobicity (log K_ow values 0.5 to 2.5), where all environmental pollutants have the utmost ability to reach biological compartments as cytosole and target sites within the membranes, to interfere with normal cell functioning by effecting normal enzymatic activity and directly to biological macromolecules.