Inhalation of prostaglandin E2 (PGE2) had been reported to prevent allergen-induced bronchoconstrictor responses; however, the effects of inhaled PGE2 on allergen-induced airway inflammation or hyperresponsiveness after allergen are unknown. This study examined the effects of inhaled PGE2 on allergen-induced airway responses and inflammation. Eight mild asthmatics with a dual airway response to inhaled allergen were recruited into a double-blind randomized crossover study comparing the effects of inhaled PGE2 (100 microgram) or placebo, on allergen-induced changes in FEV1 measured for 7 h, induced sputum inflammatory cells, obtained at baseline, 7 and 24 h, and methacholine airway responsiveness measured at 24 h after challenge. Inhaled PGE2 attenuated the allergen-induced early fall in FEV1 from 24.4 +/- 3.6% after placebo to 10.3 +/- 2.5% after PGE2 (p = 0.002), the late fall in FEV1 from 21.2 +/- 2.7% after placebo to 12.6 +/- 3.6% after PGE2 (p = 0.03), allergen-induced methacholine airway hyperresponsiveness (p = 0.03) and allergen-induced increases in percent sputum eosinophils from 36.3 +/- 8.8% after placebo to 21.0 +/- 7.3% after PGE2 (p = 0.01), percentage of EG2+ cells (p = 0.02), and percentage of metachromatic cells (p = 0.02). These results indicate that inhaled PGE2 attenuates allergen-induced airway responses, hyperresponsiveness, and inflammation, when given immediately before inhaled allergen.