Synthetic combinatorial libraries have been used for the rapid identification of new opioid ligands for the micro opioid receptor. The ligands identified have included peptides composed entirely of L- or D-amino acids, peptides composed of L- and D- amino acids and non-peptidic compounds (polyamines). Both agonists and antagonists for the micro receptor have been identified using synthetic combinatorial libraries. Neither the acetalins nor the all D-amino acid peptide bear any obvious sequence relationship to the enkephalins or to other related opioid peptides. An endogenous ligand (nociceptin) has recently been identified for the orphan opioid receptor clone (ORL). In an expansion of this study, a radioreceptor binding assay will be developed for the ORL using tritiated nociceptin as radioligand. In addition a radioreceptor binding assay will be developed using a peptide analog also encoded by the rat cDNA. It is expected that new agonists and antagonists will rapidly be identified using the combinatorial libraries successfully used in m, d, and k, receptor assay systems. Nociceptin is a heptadecapeptide with pro-analgesic activity, it is believed that antagonists to the ORL may promote analgesia. The compounds identified from combinatorial libraries will include small peptide and organic compounds, with greater stability and oral availability which will provide more useful drug candidates. The activities of these compounds will be contrasted with compounds previously obtained by screening combinatorial libraries at other opioid receptors.