The cis-trans imide isomerization reaction of the proline dipeptide is analyzed. It is shown that the reaction path is complex and involves the imide bond torsion angle omega, the pyramidalization of the imide nitrogen, and the proline backbone torsion angle psi. A virtual dihedral angle zeta is found to be better suited for describing the progress of the reaction than omega. Adiabatic energy maps are calculated as a function of these coordinates with the empirical CHARMM potential and at the 6-31G*//3-21G ab initio level. The gas phase 6-31G* activation barriers for trans --> cis isomerization from the optimized ground state to the transition state are 17.9 and 20.7 kcal/mol for the clockwise (syn) and anticlockwise (anti) path, respectively. A strong dependence of the activation barrier on psi is found; its value can change the barrier by as much as 12 kcal/mol. For psi similar to 0 degrees, the C-terninal NH group can interact with either the lone pair of the imide nitrogen (syn) or the imide carbonyl oxygen (anti); both interactions result in a lowering of the barrier. This "autocatalytic" stabilization of the transition state has implications for the mechanism of catalysis in rotamases.