Selective dopamine (DA) DA1 and DA2 receptor agonists and antagonists were examined for their effects on cold-stress gastric lesions, 100% ethanol gastric lesions and basal gastric acid secretion. The selective DA1 agonist SKF 38393 [R-(+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol.HCl] attenuated cold-stress and ethanol lesions and blocked basal acid output. The protective effects of SKF 38393 were reversed by the cyclooxygenase inhibitors indomethacin, sodium meclofenamate, by the peripherally selective DA receptor antagonist domperidone and by the tissue sulfhydryl blocker, N-ethylmaleimide. The DA1 antagonist, SCH 23390, worsened lesion formation and augmented gastric acid secretion. N-0437 [S-(-)-2-N-propyl-N-2-thienylethylamino)-5-hydroxytetralin], a DA2 agonist, was less potent than SKF 38393 at reducing experimental gastric lesion formation, but slightly more potent at attenuating gastric secretion. The DA2 antagonist, eticlopride, was inactive in all models. Based upon these in vivo data, we suggest that: 1) the gut DA receptor may be of the DA1 subtype and 2) that activation of gut DA1 receptors produces gastroprotection by several mechanisms, at least one of which is by reducing gastric acid output.