Various theoretical studies have been reported addressing the performance of solvation models available to estimate pK(a) values. However, no attention has been paid so far to the role played by the electronic, thermal and solvation energy individual contributions to the Gibbs free energy of the deprotonation process. In this work, we decompose the total Gibbs free energy into three distinct terms and then evaluate the dependence of each contribution on the level of theory employed for its determination using different levels of theory. The three possible pK(a)s of histamine have been estimated and compared with available experimental data. We found that the electronic energy term is sensitive to the level of theory and basis set, and, therefore, could be also a source of error in the theoretical calculation of pK(a)s. (C) 2003 Elsevier B.V. All rights reserved.