An investigation of the conformational profiles of two cyclic delta-selective opioid peptides, [D-Pen2,D-Pen5]-enkephalin and [D-Pen2,L-Pen5]-enkephalin, has been made. The methods and procedures used are more extensive and systematic than those previously reported, involving a combination of nested grid rotations, cyclic ring-closing algorithms, molecular dynamic simulations at high and low temperature, and total geometry optimizations. The reexamination is a necessary first step in further characterization of the bioactive form of delta-selective peptides. This study also addresses the question of how rigid such cyclic analogs actually are. Finally, the effect of solvent environment on the low energy conformers obtained from the extensive search strategy has been determined. Simulation of the effect of water as a solvent by a continuum dielectric constant of 80 results in the breaking of internal hydrogen bonds and rearrangement of the rank order of energy of the conformers. The lowest energy solution conformation for [D-Pen2,D-Pen5]-enkephalin, obtained without utilizing any experimental data, is in excellent agreement with the geometric properties deduced from its solution NMR spectra.