1. The influence of opioids in modulating gastric acid secretory responses has been investigated in the continuously perfused stomach of the anaesthetized rat. 2. Intravenous administration of morphine (0.75-3 mg kg-1) or the peripherally acting enkephalin analogue, BW443C (0.75-3 mg kg-1), substantially augmented acid secretion in basal conditions. These effects were significantly inhibited by the opioid antagonists naloxone (1 mg kg-1) and the peripherally acting N-methylnalorphine (2 mg kg-1). When administered alone, neither opioid antagonist influenced basal acid output. 3. Acid secretory responses to different levels of gastric distension (5-20 cmH2O) were significantly and dose-dependently reduced in rats pretreated with morphine (3 mg kg-1) or BW443C (1.5 mg kg-1). Previous administration of either naloxone or N-methyl nalorphine reversed the inhibitory effects of opioids on gastric acid secretion stimulated by distension. Likewise, blockade of opioid receptors with naloxone or N-methylnalorphine significantly increased acid output induced by distension. 4. Levels of serum gastrin in control animals were not increased after intragastric distension (20 cmH2O). Pretreatment with BW443C (1.5 mg kg-1) did not modify the levels of gastrin present during basal or distension stimulated conditions. 5. Pretreatment with morphine or BW443C did not influence the acid responses to i.v. injection of pentagastrin (100 micrograms kg-1), histamine (5 mg kg-1) or carbachol (4 micrograms kg-1). Acid secretion induced by i.v. administration of 2-deoxy-D-glucose (150 mg kg-1) was reduced in rats pretreated with morphine but not with BW443C. Gastric secretory responses to insulin (0.3 i.u. kg-1) were not modified by i.v. morphine.6. These observations support a role for peripherally acting opioids in the regulation of gastric acid secretion during basal and distension-stimulated conditions.