The prototropic tautomerism of xanthine (XAN) has been studied both in the gas phase and in aqueous solution by means of theoretical methods. The most stable tautomeric form has been paired with 2,6-diaminopyrimidine (DAP). The structural and energetic changes that take place on pairing have also been calculated. Applying an elimination procedure, two tautomeric forms of XAN survived, namely, N7-H and N9-H, whereas for DAP the amino form is by far the most important species and the amino-imino and diimino tautomers would not be present in appreciable concentration. In XAN, the N7-H species is more stable than N9-H by ca. 8 kcal/mol in the gas phase. The solute-solvent interactions were taken into account by applying Onsager 's simple SCRF model to the dipole term. The results indicate that the solvent does not alter the stability of these species, but reduces their energy difference to ca. 5 kcal/mol. The optimized geometries and the energetics obtained at the HF/6-31G** and MP2/6-31G** levels reveal large differences in the bonding patterns of these bases as well as lower interaction energies as compared with the natural adenine-thymine (AT) and guanine-cytosine (GC) and non-natural azaadenine-thymine (AA-T) and azaguanine-cytosine (AG-C) pairs