Hydrolyses of 54 O-acylglycolamides in aqueous base have been studied as models for the hydrolysis of acylated serine proteases. The essential feature of these models is the presence of amide residues capable of intramolecular hydrogen bonding with the carbonyl oxygen of the ester in a way similar to that proposed for the mechanism of action of serine proteases. No significant enhancement due to electrophilic participation is observed for the reactivity of the models as compared with that expected for normal substituent effects; this is explained by the strained nature of the interacting conformer as compared with that where amide and ester moieties are remote from each other. The action of the oxyanion pocket in the active site of proteases does not povide a major contribution to enzymic activity apart from an entropic factor in salvation; the electrophilic interaction is necessary to allow the formation of the oxyanion and hence the tetrahedral intermediate in the close-packed environment of the active site which would otherwise be non-polar.