The formation process of soluble complexes and insoluble aggregates between superoxide dismutase (SOD) and hyaluronic acid (HA) was studied using quasielastic light scattering and turbidimetric titration. The electrostatic binding between them was investigated in detail through potentiometric titration and turbidimetric titration carried out from high to low pH. Turbidimetric titration was used to determine the specific pH values at which soluble complex formation was initiated (pH(c)) and phase separation occurred (pH(phi)). An increase of the ionic strength causes a decrease of pH(c) and pH(phi). With the increase of HA concentrations, pH(phi), increases but pH(c). does not vary. The formed "salt bridges" between -NHS3+ (SOD) and -COO- (HA) result in the formation of stable SOD-HA complexes and even aggregates. The necessary condition of electrostatic binding was also given for protein-acidic polyelectrolyte systems. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 113: 2533-2589, 2009