At high protein concentrations (i.e. 50-100 mg/mL) and 37°C, low solution ionic strength accelerates aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra). To explain these observations, we have determined protein assembly state behavior using analytical ultracentrifugation, and combined these results with measured free energies of unfolding as a function of ionic strength, as well as second osmotic virial coefficients determined by light scattering. In addition, a population balance model was applied to aggregate growth kinetics to determine aggregate nucleation and growth rates. Activity coefficient of rhIL-1ra estimated from aggregation rates is 50 % higher at 100 mg/mL protein concentration than at 50 mg/mL, in close agreement with predictions from a hard-sphere model for activity coefficients.