The values of K-a, Delta S-a, and Delta H-a for deprotonation of hydroxyurea (HU) and N-methylhydroxyurea (NMHU), as targeted compounds, and for betainohydroxamic acid, were potentiometrically determined. Although NMHU has two and HU even three deprotonation sites, the measurements confirm that they behave as weak acids with a single pK(a) approximate to 10. Comparison with analogous thermodynamic parameters previously determined for series of monohydroxamic acids reveals deviations from a Delta S-a, vs Delta H-a plot for HU and NMHU, raising the question of the dissociation site of hydroxureas in water. In addition to the deprotonation of the hydroxyl oxygen, ab initio calculations performed at the MP2/6-311++G(d,p) level of theory for these two compounds indicate a notable participation of the nitrogen deprotonation site in HU. The calculations for the isolated, monohydrate, trihydrate, and decahydrate molecular and anionic forms of hydroxyureas support the importance of hydrogen bonding, in the gas and aqueous phases. The hydroxylamino nitrogen in HU is the most acidic site in water, contributing similar to 94% to the overall deprotonation process at 25 degrees C. On the contrary, the, almost 100% in hydroxylamino oxygen is by far the most favored deproronation site in NMHU, contributing aqueous medium. The predicted participations of two deprotonation sites in HU, calculated at the MP2/6-311++G(d,p) level of theory. combined with the calculated relative reaction enthalpy and entropy for the deprotonation, satisfactorily explain the observed deviation from linearity of Delta H-a vs Delta S-a, plot. There is no such a simple explanation for acid-base behavior of NMHU.