Low-temperature single-crystal structure determinations have been carried out on isoxazol-3-ol, 5-methyl-isoxazol-3-ol, isothiazol-3-ol and 5-methylisothiazol-3-ol, the heterocyclic ring systems used as carboxy group bioisosteres in numerous neuroactive analogues of 4-aminobutyric acid (GABA) and glutamic acid. All compounds form hydrogen-bonded dimers in the solid state. The OH ⋯ N hydrogen bonds are shorter in isoxazol-3-ols than in isothiazol-3-ols. The excess molecular van der Waals volume of the sulfur-containing ring systems as compared to the corresponding isoxazol-3-ols amounts to about 15%. The sulfur substitution significantly affects the position of the 5-substituents in relation to the heterocyclic ring. Such effects may contribute to the observed differences in pharmacological effects of the structurally related isoxazol-3-ol and isothiazol-3-ol amino acids. The geometries of the compounds have been optimized by ab initio calculations at the HF/6-31G^* level, and in some cases also at the MP2/6-311G^** level. The gas-phase calculations are in agreement with the experimental data, especially when correction for the effects of hydrogen bonding is made, as estimated using a complex between isoxazol-3-ol and formic acid. Calculated dipole moments of isoxazol-3-ols and isothiazol-3-ols are similar. Isoxazol-3-ol is more acidic than isothiazol-3-ol by 1.7 pK_a unit as determined by ¹³C NMR titration, and the differences in acidity are believed to be one of the major factors causing the differences in the biological actions of isoxazol-3-ol amino acids and the corresponding isothiazol-3-ol analogues.