An accurate estimation of pK(a) values in methanol-water binary mixtures is very important for several separation techniques such as liquid chromatography and capillary electrophoresis that use these solvent mixtures. In this study, the pK(a) values of 11 polyphenolic acids have been determined in methanol-water binary mixtures (10%, 20% and 30% (v/v)) by potentiometry, liquid chromatography (LC) and LC-DAD methodology. The results show a similar trend for the pK(a) values of all the studied compounds, as they increase with increasing concentration of organic modifier, which allows a linear relationship between pK(a) values and mole fraction of methanol to be obtained. The pK(a) values obtained in aqueous medium have been compared with those given in the literature, and also with the values predicted by the SPARC on-line pK(a) calculator. The data obtained have been used to test the feasibility of an estimation of dissociation constants in a methanol-water medium from the relationship between pK(a) values and the organic cosolvent fraction in the mixtures, (c) 2006 Elsevier B.V. All rights reserved.