The effects of ouabain, amiloride, K(+)-free solution and low Na+ (25 mM) solution on the responses to CaCl2 (in Ca(2+)-free, K(+)-depolarizing solution), KCl, acetylcholine, histamine and 5-hydroxytryptamine were studied in guinea-pig isolated trachea. Ouabain (10 microM) did not alter the contractile responses to CaCl2, KCl and acetylcholine but depressed those to histamine and 5-hydroxytryptamine produced in normal Ca2+ (2.5 mM) and Ca(2+)-free (EGTA 0.1 mM) media. Amiloride (0.1 mM), K(+)-free solution, and low Na+ solution depressed responses to acetylcholine, histamine and 5-hydroxytryptamine produced in normal Ca2+ and Ca(2+)-free media. Ouabain and amiloride had no effect on responses of skinned strips to Ca2+. The mechanism of the inhibitory effects of these interventions is uncertain but the findings suggest that the availability of Na+ influences the airway smooth muscle responses to spasmogens.