The effect of different opioids receptor agonists-morphine, DAGO (mu-agonists), DADLE, DPDPE and deltorphin II (delta-agonists)-on gastric mucosal damage induced by either acidified ethanol or acidified aspirin was studied following subcutaneous (sc) administration of these agonists. The results indicate that both mu and delta receptors are involved in gastroprotection. Morphine, DAGO and DADLE, injected intracerebroventricularly, were also effective in both ulcer models. This suggests that gastric cytoprotection can be induced also be central action, since gastric acid secretion is not involved in the pathomechanism of mucosal damage induced by acidified ethanol. Interaction between the opioids and alpha(2)-adrenoceptors in gastroprotection is suggested by the findings that the gastroprotective effect of clonidine (0.09 mumol/kg orally) was antagonized by opioid antagonists. As both naloxone (1.38 mumol/kg sc) and naltrindole (12 mumol/kg sc) exerted antagonist effects, both mu and delta receptors are likely to be involved in presynaptic alpha(2)-receptor-mediated gastroprotection.