Helicidine is a biological extract prepared from the snail Helix pomatia L. and used in man as an anti-tussive agent. However, its mechanisms of action are not fully defined. In this study, we have investigated a possible relaxant effect of helicidine on guinea-pig airway smooth muscle and evaluated the role of prostanoids and airway epithelium in this relaxation. H. pomatia extract (0.001-1 mg/ml) induced a dose-dependent relaxation of guinea-pig trachea pre-contracted with histamine both in the presence and absence of tracheal epithelium. No significant difference in dose-dependency or magnitude of the relaxation was observed between tracheal segments with or without epithelium (maximal relaxant response of 35 +/- 7 and 25 +/- 7.5%, respectively). Relaxation of the trachea induced by H. pomatia extract (0.001-1 mg/ml) was inhibited by pre-treatment with the cyclooxygenase inhibitor, indomethacin, both in the presence or absence of tracheal epithelium. H. pomatia extract (1 mg/ml) induced a marked and significant increase in prostaglandin E2 release in tracheal segments with and without epithelium. These results indicate that helicidine possesses a broncho-relaxant activity which is independent of epithelium integrity and which is partly mediated by the release of the relaxant prostanoid, prostaglandin E2. The origin of prostaglandin E2 production in the airways remains to be defined.