A human delta opioid receptor cDNA clone (pREP10/hDOR) was transfected into Chinese hamster ovary (CHO) cells. The stable cell line expressed a high density of delta opioid receptors (137,000 +/- 21,600 receptors/cell). DPDPE inhibited 90% of the forskolin-stimulated cAMP accumulation in these cells with high potency (EC50 = 1.3 nM). This effect of DPDPE was antagonized by naltrindole. The pseudo-pA2 value (Ke) of 155 pM for naltrindole is consistent with that measured for delta receptor antagonism in the mouse vas deferens. This is the first detailed characterization of DPDPE activity on forskolin-stimulated cAMP accumulation mediated through a human delta opioid receptor. The data support the use of the recombinant cell line for functional studies of opioid drugs.