BACKGROUND: In animals, activation of 5-HT(1) like receptors causes a relaxation of the gastric fundus through the activation of intrinsic inhibitory neurones. AIMS: To investigate the effect of sumatriptan, an agonist at enteric neuronal 5-HT(1) receptors, on fasting fundus tone and sensitivity to gastric distension in man. METHODS: A gastric barostat was used to study the effect of placebo and sumatriptan, 6 mg subcutaneously, on basal fundic tone in healthy subjects. In addition, stepwise isobaric and isovolumetric gastric distensions were performed and perception was measured before and after the administration of placebo and sumatriptan. RESULTS: Placebo had no significant effects on gastric tone and on perception. Sumatriptan induced an immediate relaxation of the gastric fundus, reflected by an intragastric volume increase of 209 (39) ml (p<0.0005). After sumatriptan, intragastric pressures at the thresholds for perception or discomfort were not significantly altered. However, the intragastric volumes and the corresponding calculated wall tensions at perception and discomfort thresholds were significantly increased. CONCLUSIONS: Administration of the 5-HT(1) receptor agonist sumatriptan induces a relaxation of the gastric fundus in man, allowing larger intragastric volumes before thresholds for perception or discomfort are reached. The effects of sumatriptan on the gastric fundus may have therapeutic potential in the treatment of patients with functional dyspepsia.