In the work the conformational-electronic aspects important for the functional activity of deltorphin I and deltorphin II are investigated by the methods of molecular mechanics, molecular dynamics and quantum chemistry using modern computer programs. It was established that the stability of the spatial structure of deltorphins is determined by the mutual arrangement of the pharmacophore elements: α-amino group, phenolic ring of Tyr1 residue, aromatic ring of Phe3 residue, negatively charged Asp/Glu residue groups and characterized by a specific distribution of electron density, which plays an important role in the interaction with receptor. Based on the obtained results and data of structure-function relationships, the biologically active conformations of deltorphins were assessed and a pharmacophore model was constructed for their binding to δ- receptors. It is shown that the biologically active conformations of these molecules are characterized by a semi-folded form of the main chain: in them the C-terminal fragment Val-Val-Gly-NH2, which has an elongated conformation, due to reverse turn on the Val5 residue in space is close to the N-terminal helical fragment Tyr-D -Ala-Phe-Asp/Glu, that makes these molecules compact. It can be assumed that for the analgesic action of deltorphins the sterically probable spatial structures of their N-terminal physiologically active tetrapeptide fragment which are stabilized by salt bridges between the protonated nitrogen atom and the oxygen atoms of the side chains of negatively charged Asp/Glu residues are responsible, while binding to the receptors is formed by the formation of hydrogen bonds with involving ionizable functional groups.