The interaction between dextran sulfate (DxS), of different charge density, and three cationic amphiphiles varying with respect, to hydrophobicity, was investigated by means of equilibrium dialysis and surface tension. The hydrophobicity of the amphiphilies studied increases in the order doxepin-HCl < amitriptyline-HCl < clomipramine-HCl, Dextran sulfate samples with five different charge densities, 0.07, 0.43, 0.7, 1.3, and 1.6 charges per monosachride, were used. The data from both methods clearly indicate that the polyelectrolyte-amphiphile interaction shows a cooperativity that starts at a certain amphiphile concentration and which depends on both the hydrophobicity of the amphiphile and the charge density of the dextran sulfate. A change in the charge density of dextran sulfate and/or amphiphile hydrophobicity affects both the onset of the cooperativity of the interaction and the degree of the cooperativity. The results have also been compared with the data published on related systems.