Abstract Saligenin cyclic phosphonates, phosphates and N-alkylphosphoramidates readily phosphorylate α-chymotrypsin at the hydroxyl group of serine-195. The phosphoenzyme undergoes rapid further reaction (aging) both to release saligenin and form bound phenolic residues without regeneration of esteratic activity. The bound phenolics include about equal parts of trapped saligenin, possibly in the region of the active site, and material which may result from enzyme alkylation. The ratio between these types of bound phenolics is altered by pretreatment of the enzyme with ethoxyformic anhydride but not with diisopropyl-fluorophosphate. N- e2 of the imidazole portion of histidine-57 may participate in the aging reaction by stabilizing a potential benzyl carbonium ion intermediate. This intermediate is subsequently trapped either by a hydroxyl nucleophile to produce saligenin or possibly by the stabilizing imidazole to yield N-alkylated enzyme. Trypsin with an esteratic site similar in configuration to chymotrypsin undergoes analogous phosphorylation and aging reactions.