Compared to most alpha-amino acids, N,N-dialkylated alpha-amino acids are very soluble in a wide range of solvents. As a result, N-alkylated amino acids are ideal for the study of the effects that substituents have on the tautomeric equilibrium of amino acids. The ratios of zwitterionic and un-ionized tautomers for nine N,N-dimethylamino acids [(CH3)(2)NCH(CR(3))COOK] were determined by NMR spectroscopy in DMSO-d(6). Compared to dimethylalanine, the tautomeric equilibrium for dimethylamino acids, where R represents alkyl groups, favors the formation of the un-ionized tautomers. For all dimethylamino acids studied, a cyclic intramolecular hydrogen bonded conformer is proposed for the zwitterionic tautomers. For the dimethylamino acid in which R represents hydrogens (dimethylalanine), the zwitterion exists as a stable eclipsed conformer with a very effective hydrogen bond. On the other hand, if R represents alkyl groups, the zwitterionic conformers are not as stable as that of dimethylalanine owing to a distortion of the hydrogen bond which is caused by the presence of the alkyl groups. Since effective solvation of the zwitterions requires that solvent molecules access the region between the charges, zwitterionic conformers in which R represents alkyl groups are less solvated than those where R represents hydrogens. As a result, substituent steric and solvation effects on the stability of the zwitterions play decisive roles on the relative magnitude of the tautomeric equilibrium of amino acids.