The role of thermal unfolding as it pertains to thermodynamic properties of proteins and their stability has been the subject of study for more than 50 years. Moreover, exactly how the unfolding properties of a given protein system may influence the kinetics of aggregation has not been fully characterized. In the study of recombinant human Interleukin-1 receptor type II (rhuIL-1R(II)) aggregation, data obtained from size exclusion chromatography and differential scanning calorimetry (DSC) were used to model the thermodynamic and kinetic properties of irreversible denaturation. A break from linearity in the initial aggregation rates as a function of 1/T was observed in the vicinity of the melting transition temperature (T-m 53.5 degrees C), suggesting significant involvement of protein unfolding in the reaction pathway. A scan-rate dependence in the DSC experiment testifies to the nonequilibrium influences of the aggregation process. A mechanistic model was developed to extract meaningful thermodynamic and kinetic parameters from an irreversibly denatured process. The model was used to simulate how unfolding properties could be used to predict aggregation rates at different temperatures above and below the Tm and to account for concentration dependence of reaction rates. The model was shown to uniquely identify the thermodynamic parameters Delta C-p (1.3 +/- 0.7 kcal/mol-K), Delta H-m (74.3 +/- 6.8 kcal/mol), and T-m with reasonable variances.