The change in free energy of binding of hen egg white lysozyme (HEL) to the antibody HyHel-10 arising from ten point mutations in HEL (D101K, D101G, K96M, K97D, K97G, K97G, R21E, R21K, W62Y, and W63Y) was calculated using a combination of the finite difference Poisson-Boltzmann method for the electrostatic contribution, a solvent accessible surface area term for the non-polar contribution, and rotamer counting for the sidechain entropy contribution. Comparison of experimental and calculated results indicate that because of pKa shifts in some of the mutated residues, primarily those involving Aspartate or Glutamate, proton uptake or release occurs in binding. When this effect was incorporated into the binding free energy calculations, the agreement with experiment improved significantly, and resulted in a mean error of about 1.9 kcal/mole. Thus these calculations predict that there should be a significant pH dependence to the change in binding caused by these mutations. The other major contributions to binding energy changes comes from solvation and charge charge interactions, which tend to oppose each other. Smaller contributions come from nonpolar interactions and sidechain entropy changes. The structures of the HyHel-10-HEL complexes with mutant HEL were obtained by modeling, and the effect of the modeled structure on the calculations was also examined. ''Knowledge based'' modeling and automatic generation of models using molecular mechanics produced comparable results. Proteins 33:39-48, 1998.