A kinetic study on the thermal denaturation accompanying precipitation of hen egg-white lysozyme was performed at temperatures between 50 and 90 degrees C. Visible precipitation occurred at lysozyme concentrations higher than 10(-5)M. Even at the concentration of 10(-6)M where no visible precipitation was observed, irreversible and reversible denaturation could be clearly discriminated. The former involves two different reactions with activation energies of approximately 93 and 50 kJ mol(-1). On the other hand, enthalpy and entropy changes in the latter are 443 kJ mol(-1) and 1280 J K-1 mol(-1), respectively, indicating a large conformational change. The contradiction that the denaturation or deactivation reaction fitted first-order reaction kinetics while its rate constant depended on the protein concentration, was resolved by newly proposed schemes. The apparent first-order rate constant obtained experimentally depended on the initial protein concentration being on the order of almost unity. Moreover, it was revealed that the apparent first-order reaction involved a second-order reaction that characterized the aggregation of denatured protein molecules. The theory developed here explained reasonably the thermal denaturation accompanying precipitation that occurs at high protein concentration and at high temperature, and was also successfully applied to the lower concentration range with no accompanying precipitation.