Dermenkephalin, H-Tyr-(D)Met-Phe-His-Leu-Met-Asp-NH2, a highly potent and selective delta-opioid peptide isolated from frog skin, was studied in DMSO-d6 solution by two-dimensional nmr spectroscopy, including the determination of NH temperature coefficients, the evaluation of 3J coupling constants from phase-sensitive correlated spectroscopy (COSY) and the volumes of nuclear Overhauser effect (NOE) correlations. The two-dimensional NOE spectroscopy (NOESY) spectrum of dermenkephalin revealed sequential, medium-, and long-range effects. To put this information on a quantitative basis, special attention was devoted to J cross-peak suppression, quantification of the NOE volumes and analysis of the overlaps, normalization of the NOEs against diagonal peaks and H beta beta' geminal interactions. Although most of the dihedral angles deduced from the 3JN alpha coupling constants together with several Ni alpha i and alpha iNi+1 NOEs pointed to a partially extended peptide backbone, several NiNi+1 NOEs and beta iNi+1 interactions argued in favor of a folded structure. Moreover, several long-range correlations of strong intensities were found that supported a close spatial proximity between the side chains of D-Met2 and Met6, Tyr1 and His4, Tyr1 and Asp7, and His4 and the C-terminal amide group. In Phe, the g- rotamer in the side chain is deduced from the 3J alpha beta coupling constants and alpha beta and N beta NOE correlations. Whereas the amide proton dependency was not indicative of stable hydrogen bonds, the nonuniform values of the temperature coefficient may reflect an equilibrium mixture of folded and extended conformers. The overall data should provide realistic starting models for energy minimization and modelization studies.