The effects of vanadate on the contractility of the guinea-pig isolated trachea was examined. Vanadate (0.1 mM) produced a sustained contraction that was abolished in Ca(2+)-free EGTA (0.1 mM)-containing physiological salt solution but was resistant to verapamil (1 microM). Vanadate (0.1 mM) depressed tracheal responses to CaCl2 (in Ca(2+)-free depolarizing solution), KCl, acetylcholine, histamine and 5-hydroxytryptamine. For vanadate (10 microM), the inhibition of spasmogenic responses only reached statistical significance for histamine and 5-hydroxytryptamine. Caffeine (1 mM)-induced spasm (trachea at 20 degrees C in the presence of indomethacin (2.8 microM)) was not affected by vanadate (10 microM-0.1 mM). Vanadate (0.1 mM) slightly depressed the responses to KCl (50 mM), acetylcholine (1 mM), histamine (1 mM) or 5-hydroxytryptamine (0.1 mM) observed in Ca(2+)-free EGTA (0.1 mM)-containing physiological salt solution. Vanadate (0.5 mM) depressed Ca2+ (20 microM)-induced contraction of trachea which had been chemically skinned of its plasmalemmal membranes. The mechanism of the inhibitory effect of vanadate on tracheal responses to a variety of spasmogens remains obscure, but, under in-vitro conditions, vanadate clearly does not induce hyper-reactivity of airway smooth muscle to spasmogens.