Succinyl phosphate reacts rapidly with the thiol N-acetyl-beta-mercaptoethylamine (a CoA analog) to form the succinate thiol ester. This is a chemical model for the enzymic reaction of CoA transferase. It is demonstrated that: 1) the chemical reaction is stepwise, proceeding through the formation of a succinic anhydride intermediate. The rate-determining step at pH 6.6 is anhydride formation. 2) The apparent equilibrium constant for anhydride formation from succinyl phosphate is increased 6000-fold in going from pH 6.6 to 4.4. Formation of the reactive anhydride intermediate is so favorable at pH 4.4 that it accumulates in the reaction solution. 3) The rate constant for anhydride formation is accelerated 60-fold in going from pH 6.6 to 4.4 due to protonation of the phosphate moiety of succinyl phosphate, which enhances its leaving ability. 4) Anhydride formation through intramolecular reaction of the --COO- group of succinyl phosphate is accelerated greater than or equal to 10(5)-fold compared to the intermolecular reaction of 1 M acetate and acetyl phosphate. Thus, in the chemical reaction, anhydride formation can be made rapid and favorable by: 1) making the reacting groups intramolecular; and 2) catalyzing the expulsion of the leaving group. These are modes of rate acceleration that can occur in enzymic reactions. This model study provides support for a mechanism that proceeds through an anhydride intermediate in the enzymic reaction catalyzed by CoA transferase.