An experimental analysis is presented of the molecular interactions controlling the activity and solubility of chlorinated dibenzo-p-dioxins (PCDDs) in water. For this purpose, the enthalpy, entropy and free-energy contributions of fusion, vaporization, solvation and aqueous solution are determined. It is shown that, due to enthalpy-entropy compensation in the water, the solvation of hydrophobic organic chemicals in water is independent of molecular size, total surface area or molar volume. The observed relationship between the aqueous solubility and molar volume (or total surface area) is caused by the phenomenon that, with increasing molar volume, molecules require more energy to leave the pure (subcooled liquid) phase. This suggests that the relationship between aqueous solubility and molecular structure, and, consequently, many quantitative structure-activity relationships (QSARs) for hydrophobic organic substances, reflect molecular interactions between the solute molecules in the pure subcooled liquid phase rather than solute-water interactions.