The ability of the natural selective delta opioid receptor agonist, [D-Ala2]deltorphin II (DADELT II), to inhibit the diarrhea induced by castor oil and colonic glass bead expulsion, was studied in rats after supraspinal and spinal administration. When injected intracerebroventricularly, DADELT II (0.2, 1, 10 micrograms/rat) inhibited diarrhea and colonic bead expulsion in a dose-related fashion but did not affect the rate of small intestine transit. Similar results were obtained when the same dose of DADELT II was administered spinally. The antidiarrheal and colonic antipropulsive effects of supraspinally and spinally DADELT II were partially or completely antagonized by subcutaneous pretreatment with 1 and 10 mg/kg, respectively, of naltrindole, a selective delta opioid receptor antagonist. These findings indicate that, in the rat, supraspinal and spinal delta opioid receptors play a role in modulating diarrhea and colonic propulsion and that DADELT II is a useful tool for investigating the role of the delta opioid system in gastrointestinal function.