Morphine potentiated the ulcerogenic activity of indometacin in a dose-dependent manner when administered subcutaneously (2.5-7.5 mg/kg). However, in the case of intracerebroventricular administration, morphine failed to exert any potentiating action. Atropine (0.5 mg/kg, s.c.) and cimetidine (12.5-25 mg/kg, s.c.) decreased the ulcerogenic activity of indometacin, and the combination of indometacin/morphine in about the same degree. However, the reduced ulcerogenic activity of indometacin after atropine or cimetidine treatment could still be enhanced by morphine if it was added to the combination of indometacin/atropine or indometacin/cimetidine. Since the potentiating action of morphine was completely blocked by naloxone (1 mg/kg), this action of morphine might be mediated via opiate receptors.