Static and dynamic light scattering were employed to determine simultaneously the average relative molecular mass, M-r, and the average hydrodynamic radius, R-h, of protein molecules. The new method was applied to the association dissociation equilibrium of apolipoprotein A-1 (Apo A-1) and its thermal unfolding. As a control, lysozyme was measured as a nonassociating protein. Apo A-1 forms oligomers as a function of concentration and temperature, and the equilibrium can be described by a cooperative association model, consisting of a nucleation step and a growth step. At concentrations of 1 and 2.7 mg/mL, the Apo A-1 solution contained mainly monomers and octamers, with intermediates occurring at very low concentrations. Oligomer formation was maximal at 22 degrees C and was characterized by a temperature-dependent association constant. The cooperative association model allows the quantitative analysis of both the average relative molecular mass, M-r, and the average hydrodynamic radius, R-h, with the same set of model parameters which, in turn, are also applicable to analytical ultracentrifugation experiments. The light scattering experiments were reversible as long as the Apo A-1 solution was not heated above 60 degrees C.