As a simple model for the hydrolysis of peptides mediated by the cysteine proteases, 2-(mercaptomethyl)1-methylimidazole (1) was used to catalyze the hydrolysis of four nonactivated amides, namely, formamide, dimethylformamide, N-formylmorpholine, and formanilide (3a-d), at 98 degrees C, pD 7.6-8.0, mu = 1.0 (KCl). Progress of the hydrolysis reactions was followed by H-1 NMR, and the kinetics as a function of added II] were used to determine the second-order catalytic rate constants (k(cat)). A putative intermediate S-formyl thiolester of 1 (4) was not observed to build up during the course of the hydrolysis : the partitioning of authentic 4 between H2O and morpholine and between H2O and aniline was determined (98 degrees C, pD 8.0). The hydrolysis of N-formylmorphline was observed to be catalyzed by added phosphate buffer under the same conditions. When the hydrolysis of a 200 mM D2O solution of N-formylmorpholine was allowed to proceed to completion, an equilibrium position of 33 mM amide, 167 mM HCO2H, and 167 mM morpholine was attained : that same equilibrium position was obtained starting with a solution 200 mM in each of HCO2H and morpholine. The conditional equilibrium constant, K’(eq) = [NFM]/([HCO2H](tot)-[morpholine](tot)), was found to be 1.2 M(-1).