A molecular-thermodynamic analysis of protein partitioning in an aqueous two-phase system shows that the partition coefficient for a native (globular) protein is very much different from that for a denatured (linear) protein; while the former is weakly dependent on protein molecular weight, the latter depends strongly on molecular weight. The native protein and the denatured protein are represented, respectively, by a spherical macroion and by a linear flexible polyion. On the basis of McMillan-Mayer solution theory, the interactions between particles are represented by a continuum-averaged potential of mean force containing hard-sphere repulsion, the effect of penetration or hydration forces, electrostatic interactions, osmotic attraction, and specific interactions. Phase diagrams are calculated for polymer-polymer and for polymer-salt aqueous two-phase-forming systems in good agreement with experiment. Coupled with measured data for obtaining model parameters, partition coefficients are calculated for a native protein, lysozyme. Calculated partition coefficients for a denatured protein are compared with experimental partitioning data for short peptides. Calculated results are remarkably similar to those observed.