A decrease in the osmolarity of the periciliary fluid of central airways is supposed to be the initiating mechanism by which ultrasonically nebulised distilled water (UNH2O) induces bronchoconstriction in asthmatics. It is therefore possible that substances, such as frusemide (F), which, in vitro, interfere with ions and water translocation across the tracheo-bronchial epithelium, can also modify such response. To test this hypothesis, 16 adult asthmatics were challenged with UNH2O after being pretreated with either inhaled F (approximately 28 mg delivered into the mouth) or placebo (the diluent) administered in random order and double-blind by means of a jet nebuliser. F did not modify baseline FEV1 and sRaw but attenuated markedly their changes after UNH2O. Mean max % (95% CI) sRaw increases after placebo and F were 293% (168-419) and 63% (21-104), respectively; mean max % falls in FEV1 were 26% (20-32) and 6% (-1-12). Thus inhaled F is highly effective in preventing UNH2O-induced bronchoconstriction and this unexpected property could have therapeutic implications.