The development of selective δ-opioid receptor agonists has revealed some very intriguing behavioral properties. δ-Opioid agonists have antinociceptive, seizuregenic and convulsive properties. A number of studies have identified a novel behavioral effect of δ-opioid-receptor agonists, implicating a role for the δ-opioid receptor in depression. Early clinical experiments demonstrated that exogenously administered opioid peptides had antidepressant activity in human patients. Also, enkephalinase inhibitors, which prevent the degradation of endogenous enkephalins, produced antidepressant-like effects mediated through the δ-opioid receptor in animal models of depression. More recently, the selective non-peptidic δ-opioid agonists SNC80 and (+)BW373U86 demonstrated antidepressant-like activity in the forced swim assay in rats. These studies propose that the δ-opioid receptor may provide a new therapeutic target for treating human depression.