During the final testing stage of a genetic algorithm based global search procedure, designed to determine low energy conformations of oligopeptides, in the gas phase we found two significantly different conformations of Leu-enkephalin with similar lowest energy values. Both conformers have been previously reported as being the global minimum for this pentapeptide. These structures differ by 0.135 kcal/mol and have an all atom RMS of 3.2 Å. One of these conformers was reported by Glasser and Scheraga (J. Mol. Biol., 199 (1988) 513) using the diffusion equation method, and the other was reported by Klepeis and Floudas (J. Comput. Chem. 20 (1999) 636) using a deterministic Branch and Bound method. Both papers report use of the ECEPP energy function. However, there is no further report that will help in clarifying which one of these two low energy conformations for Leu-enkephalin is the true global energy minimum within the ECEPP formalism. It is known that the bottom of the energy well of protein empirical potentials is rugged and that it allows the coexistence of many conformers. The questions are whether these conformers have similar or different secondary structure parameters, and which one of these corresponds to the global energy minimum. To help solve this crux we reevaluated the potential energy of the two Leu-enkephalin structures mentioned above with different force fields, with and without solvent effects. The results indicate that the structure reported by Glasser and Scheraga is the most stable conformer for Leu-enkephalin. © 2001 Elsevier Science B.V. All rights reserved.