Our overall objective is to identify the microscopic molecular factors which produce the scattering elements responsible for lens opacification. These elements are high molecular weight protein aggregates, and spatially segregated protein-rich and protein-poor domains produced by phase separation. To achieve this objective we propose the following lines of investigation. 1. To determine the location of phase boundaries and the equation of state for aqueous solutions of highly purified alpha, beta and gamma crystallins and mixtures of these for fixed physiological solution conditions. 2. To determine the effect of changes in solution conditions such as pH, and ionic strength and ion identity on the location of phase boundaries and the equation of state for the lens protein solutions above. 3. To evaluate the consequences of specific covalent modifications on the location of phase boundaries and the formation of high molecular weight aggregates in two- component and multi-component protein solutions. 4. To determine the effect of noncovalently binding ligands on the location of the phase boundaries in two-component and multi-component protein solutions. 5. To use the data on equation of state and phase boundaries obtained above to determine the factors which control osmotic water balance within the lens. 6. To obtain a quantitative theoretical understanding of the structure of the Gibbs free energy which can predict the equilibrium properties of the lens protein solutions studied.