The nitrogen isotopic reduced partition function ratio (RPFR) of glycine (Gly) and serine (Ser) in water has been evaluated by a couple of methods. The experimental fact that those amino acids are present in the zwitterionic form in water has been best reproduced when trihydrated Gly and Ser molecules were treated by the discrete microsolvation method coupled with the self-consistent reaction field (SCRF) approach. The RPFR values of Gly and Ser in water at 25 °C are evaluated as 1.11152 and 1.11070, respectively, and the equilibrium constant of the nitrogen isotope exchange reaction between the two amino acids is calculated as 1.0007 ± 0.0008 at 25 °C. Equivalent results may be obtained by the SCRF method for non- and monohydrated molecules in the zwitterionic form.