N-methylacetamide (NMA) served as a model to investigate the hydrolysis kinetics and mechanism of N-substituted amides in high-temperature water. The major products are acetic acid and methylamine, and the reaction is reversible. The hydrolysis reaction is first order in water and first order in NMA at both subcritical and supercritical conditions. The hydrolysis rate is also pH dependent, and three distinct regions of pH dependence exist. At low and high pH, the conversion increased rapidly with added acid and base, respectively. At near-neutral pH, however, the rate was essentially insensitive to changes in pH. Further investigation revealed that the hydrolysis rate constant was very sensitive to the size of the substituent on the carbonyl carbon atom. An S(N)2 mechanism with water as the nucleophile appears to be a likely candidate for the hydrolysis mechanism in high-temperature water at near-neutral conditions. (C) 2009 Elsevier B.V. All rights reserved.