Extensive research over two decades has established the existence of μ, δ, and κ opioid receptor types and their subtypes, with highly selective ligands playing a central role in their identification and functional elucidation. New, potent and selective nonpeptide δ opioid receptor agonists, antagonists, affinity labels, and imaging agents are required to advance understanding of their roles in CNS disorders, drug-seeking behavior, and the development of new medications. A novel racemic nonpeptide δ opioid receptor agonist, BW373U86 [(±)-1], has emerged as a key template, but studies of its optically pure enantiomers are essential due to the distinct pharmacological effects of drug enantiomers. We report the synthesis and absolute configuration of the optically pure enantiomers of phenolic 1, its benzylic epimer 10, and their methyl ethers 8 and 9. Evaluation of these compounds shows that the nonphenolic (+)-8 (SNC 80) exhibits remarkable δ/μ selectivities of approximately 2000-fold in both receptor binding and bioassays (mouse vas deferens [MVD] and guinea pig ileum [GPI]). In conclusion, a practical synthesis and initial biological characterization of optically pure isomers of (±)-1 and related compounds are described. The data indicate that (+)-8 is a highly selective and potent nonpeptide δ agonist with ~2000-fold δ/μ selectivity in both binding and bioassays. (+)-8 and related compounds can complement molecular studies of δ receptor interactions with (±)-1, providing valuable insight into the roles of opioid receptor subtypes in drug-seeking behavior, antinociception, tolerance, dependence, and addictive diseases. Structure-activity relationship studies using (+)-8 as a template are ongoing to develop highly selective affinity labels, imaging agents, and other research tools.