The process of irreversible thermal denaturation of macromolecules involves cooperative bond breakage. Many bonds must break at the same time to allow denaturation. Hence, molecules are stabilized against thermal damage. However, these multiple bonds enforce a structural order on the macromolecule. A review of the literature on the entropy &Dgr;S (J/(mole K)) and enthalpy &Dgr;H (J/mole) of various endpoints of irreversible thermal denaturation (eg., whitening, contraction, loss of birefringence, necrosis, onset of heat shock proteins) indicate that the ratio &Dgr;S/&Dgr;H is constant at a value of 31.47x10-4 K-1, or 1/Tcrit where Tcrit ≈ 44.6°C. The free energy of denaturation is &Dgr;G = &Dgr;H - T&Dgr;S. At temperatures below Tcrit, more cooperative bonds yield more stability because &Dgr;H dominates over T&Dgr;S, but at temperatures above Tcrit more bonds yield less stable structure because T&Dgr;S dominates over &Dgr;H. Only one free parameter describes the kinetics of irreversible denaturation of macromolecules involving simultaneous breakage of multiple cooperative bonds, the &Dgr;H of the transition.