High level quantum chemistry calculations have been applied in order to explore the intramolecular proton transfer process in the tautomers of adenine. The presence of hydration water stabilizes the imino form of the tautomers of adenine by approximately 2-3 kcal/mol. Inclusion of the bulk electrostatic interaction lowers the relative energy of A(am)N(7)H and A(am)N(7)H . H2O to only approximately 4 kcal/mol above A(am)N(9)H and A(am)N(9)H . H2O. Consequentely, A(am)N(7)H might be present in a relatively large concentration in aqueous solutions and biological systems. The activation free energy for the transition of A(am)N(9)H . H2O to TS1 . H2O and for A(im)N(9)H . H2O to TS1 . H2O are 18.0 and 8.6 kcal/mol, while without water assistance, the free energy differences between A(am)N(9)H and TS1 as well as A(im)N(9)H and TS1 are 45.2 and 32.6 kcal/mol, respectively. The activation free energy for the N(7)H form is reduced to 16.1 kcal/mol for the transition of A(am)N(7)H . H2O to TS2 . H2O and is reduced to 9.7 kcal/mol for the transition of A(im)N(7)H . H2O to TS2 . H2O. A lower activation energy barrier suggests that thermodynamics might control the tautomeric equilibrium. The inclusion of quantum mechanical tunneling effects in the calculations dramatically increases the proton transfer rate in adenine, The tunneling rates were evaluated to be 10(10) times larger than the classical one for the gas phase and 10(3)-10(4) times larger than for the classical proton transfer rate for the water-assisted process, suggesting the importance of the tunneling effect in the intramolecular proton transfer in the tautomers of adenine.