Experiments and computer simulation show that the uranium enrichment factor in redox chromatography is determined substantially by electron exchange, isotope adsorption-desorption, and oxidation state adsorption-desorption equilibria. Computer simulation utilizing the theoretical model closely predicts the difference between the value of an enrichment factor derived from the solution equilibrium and that observed in the chromatographic isotope separation, which is attributable to a biased distribution of uranium ions between the solid and liquid phases and a nonequilibrium state in the separation column, thus allowing elucidation of the separation mechanism. A theoretical description of the central role of this enrichment factor in determining plant size and economics is presented.