The decarboxylation of N-carboxy-2-imidazolidinone has previously been established as a model for the transfer of carbon dioxide from N(1’)-carboxybiotin. The present paper reports the pH-dependence of the reaction as well as the acceleration of the reaction in methanol and in acetonitrile. These results suggest that enzymic reactions of N(1’)-carboxybiotin in a hydrophobic active site with decreased hydrogen bonding can be rapid if the energy of desolvation is compensated by the energy made available by association of the substrate and protein. In addition, a report on the decarboxylation of N-carboxy-2-imidazolidinone in organic solvents containing macrocycles (Kluger, R.; Tsao, B. J. Am. Chem. Sec. 1993, 115, 2089-90) must be reinterpreted on the basis of the inherent instability of the substrate under the reaction conditions.