We performed a double-blind, two-phase study on protective and bronchodilator effects of prostaglandins E2 and E1 (PGE2, PGE1) and salbutamol in patients with aspirin-induced asthma (AIA). In phase 1 we assessed the effects of pretreatment with PGE2, salbutamol, or the PGE1-analogue, misoprostol, on bronchoconstriction precipitated by inhalation of L-lysine aspirin in 11 patients with AIA. PGE2 and salbutamol were inhaled at equimolar concentrations of 0.25 mumol, 5 min before the aspirin challenge, while 400 micrograms misoprostol was administered orally 1 h before challenge. PGE2 attenuated the bronchoconstrictive reactions in 10 patients, salbutamol in eight, and misoprostol in seven. The mean provocative dose of aspirin causing a 20% fall in FEV1 (PD20) decreased after PGE2 (p = 0.04) and salbutamol (p = 0.06), but only marginally after misoprostol (p = 0.25). There was a positive correlation between magnitude of the protection offered by the three compounds in individual subjects. In phase 2, we examined bronchial response to inhaled PGE2, PGE1, salbutamol, and 2% ethanol in 12 AIA patients compared with 10 aspirin-tolerant patients with asthma. AIA subjects were characterized by less pronounced and shorter bronchodilator responses. There was no correlation between the protective and bronchodilator actions of the compounds used in individual patients. Thus, inhaled PGE2 and salbutamol protect against aspirin-induced attacks of asthma through mechanisms unrelated to their bronchodilator properties. Airways of aspirin-sensitive patients with asthma demonstrate distinct bronchial reactivity.