The two structurally different peptides DPDPE and Dermenkephalin show a similar remarkably high affinity and selectivity for the delta opioid receptor subtype. An effort has been made to gain some insight into the factors responsible for the recognition ability of these two molecules by synthesizing some DPDPE-Dermenkephalin peptide hybrids and some conformationally restricted Dermenkephalin analogues. The results of the binding and the in-vitro bioassays have been compared with those of the parent peptides. A general decrease in receptor affinity has been observed in the peptide hybrids while the dermenkephalin analogues have shown a wider range of affinities and selectivities. The above findings contribute to the understanding of the structural requirements of the delta receptor, provide information about the sensitivity of Dermenkephalin to enzymatic degradation, and indicate directions for future research