The neutralization of CH 3 COOH by NaOH in water has been studied by the mass spectrometric analysis of clusters generated via fragmentation of liquid droplets. In water, CH 3 COOH molecules form self-association clusters at higher acid concentrations like the molar ratio of CH 3 COOH:H 2 O=1:10. At these concentrations, the neutralization takes place via interaction between the CH 3 COOH clusters and NaOH to afford Na + (CH 3 COOH) a (CH 3 COONa) b clusters. Furthermore, Na + is preferentially solvated by CH 3 COOH in water to form Na + (CH 3 COOH) α clusters. In consideration with these cluster structure, the reaction mechanism in solution can be realized more precisely.