Evaluation of the free energy of ionization of acidic groups in proteins may be used as a powerful and general test case for determining the reliability of calculations of electrostatic energies in macromolecules. This work attacks this test case by using an adiabatic charging process that evaluates the changes in free energies associated with ionizing the acidic groups Asp-3 and Glu-7 in bovine pancreatic trypsin inhibitor and aspartic acid in solution. The results of these free energy calculations are very encouraging; the error range is about 1 kcal/mol for these free energy changes of about-70 kcal/mol. This indicates that we are finally approaching the stage of obtaining quantitative results in modeling the energetics of solvated proteins.