Understanding the pharmacology of opioid receptors took a major step forward with the cloning of genes that encode four members of the opioid receptor family. Gavril Pasternak and Kelly Standifer show how strategies that use antisense oligodeoxynucleotides can provide a selective approach to correlate the properties of the cloned receptors with their in vivo pharmacological effects, and have confirmed the association of the delta-, mu- and kappa 1-opioid receptor clones with analgesia mediated through delta-, mu- and kappa 1-opioid receptors, respectively. Approaches that use antisense oligodeoxynucleotides provide an opportunity to characterize the pharmacology of short cDNA fragments without necessitating the cloning of the entire cDNA and can assess the role of the products of specific exons in a receptor, providing an approach for the study of alternative splicing as demonstrated with the mu- and kappa 3-opioid receptor clones.