Nonsteroid antiinflammatory drugs interfere with the diuretic activity of furosemide, implying that this effect is at least partially dependent on renal prostaglandin synthesis. To investigate whether prostaglandin production could also modulate the bronchial antireactive activity of this diuretic drug, we investigated the effect of inhaled lysine acetylsalicylate (162 mg) and of furosemide (18 mg), alone and in combination, on the bronchial obstructive response to ultrasonically nebulized water in asthmatic patients. The study was also prompted by the conflicting results obtained in previous studies of oral nonsteroid antiinflammatory drugs. Fifteen asthmatic patients underwent bronchial challenge with a mist of ultrasonically nebulized distilled water at the same time of day on four occasions, 2-4 days apart, 15 min after premedication according to a double-blind, randomized protocol. After placebo, mean PD15 to water mist did not differ from a preliminary test (2.1 +/- 0.2 and 2.5 +/- 0.4 ml, M +/- SE, respectively). After lysine acetylsalicylate, mean PD15 rose to 5.0 +/- 0.7 ml (2.8 +/- 0.6 times higher than placebo); after furosemide, to 9.0 +/- 1.5 ml (4.4 +/- 0.9 times over placebo); and after the two drugs in combination, to 32.2 +/- 5.6 ml (16.3 +/- 3.0 times higher than placebo). Similar results were obtained with inhaled indomethacin, whereas sodium salicylate had no effect. These data indicate that the bronchial antireactive activity of inhaled furosemide is greatly enhanced by inhaled lysine acetylsalicylate through a mechanism which probably involves inhibition of the local synthesis of prostaglandins, and could have therapeutic implications.