A novel model linking the thermodynamics and kinetics of hemoglobin's allosteric (R → T) and ligand binding reactions is applied to photolysis data for human HbCO. To describe hemoglobin's kinetics at the microscopic level of structural transitions and ligand-binding events for individual [ij]-ligation microstates (ijR → ijT, ijR + CO → (i+1)kR, and ijT + CO → (i+1)kT), the model calculates activation energies, ijΔG‡, from previously measured cooperative free energies of the equilibrium microstates (Huang, Y., and Ackers, G. K. (1996) Biochemistry 35, 704−718) by using linear free energy relations (ijΔG‡ − 01ΔG‡ = α[ijΔG − 01ΔG], where the parameter α, describing the variation of activation energy with reaction energy perturbation, can depend on the natures of both the reaction and the perturbation). The α value measured here for the allosteric dynamics, 0.21 ± 0.03, corresponds closely to values observed previously, strongly suggesting that the thermodynamic microstate energies directly underlie the allosteric kinetics (as opposed to the α(ijΔGRT) serving merely as arbitrary fitting parameters). Besides systematizing the study of hemoglobin kinetics, the utility of the microstate linear free energy model lies in the ability to test microscopic aspects of allosteric dynamics such as the “symmetry rule” for quaternary change deduced previously from thermodynamic evidence (Ackers, G. K., et al. (1992) Science 255, 54−63). Reflecting a remarkably detailed correspondence between thermodynamics and kinetics, we find that a kinetic model that includes the large free energy splitting between doubly ligated T microstates implied by the symmetry rule fits the data significantly better than one that does not.