Cyclooxygenase products modulate the expression of nitric oxide synthase (NOS) in certain cell types. We determined the effect of prostaglandins (PG) E2 and F2alpha on exhaled nitric oxide (NO) concentrations measured by chemiluminescence. Inhaled PGE2 and PGF2alpha significantly reduced exhaled NO. After the highest dose of PGE2 (100 micrograms), NO concentrations fell from 6.9 +/- 0.5 ppb to 4.0 +/- 0.8 ppb (p < 0.001), and from 22.9 +/- 2.0 ppb to 12.3 +/- 1. 2 ppb (p < 0.001), whereas after PGF2alpha, it fell from 6.5 +/- 0.6 ppb to 3.0 +/- 0.5 ppb (p < 0.001), and from 26.0 +/- 3.4 ppb to 11. 5 +/- 1.4 ppb (p < 0.001) in normal (n = 7) and asthmatic (n = 8) subjects, respectively. Although the prostaglandins did not change FEV1 in normal subjects, PGE2 caused an increase in asthmatics (from 3.6 +/- 0.3 L to 3.8 +/- 0.4 L, p < 0.05) and PGF2alpha caused a transient reduction in FEV1 from 4.0 +/- 0.2 L to 3.5 +/- 0.2 L (p < 0.05). To further determine the relationship between bronchoconstriction and exhaled NO levels, we examined the effect of inhaled methacholine which did not change exhaled NO concentrations in normal and asthmatic subjects despite a greater than 20% fall in FEV1 in asthmatics. Therefore, PGE2 and PGF2alpha reduce exhaled NO, an effect not related to airway caliber changes but which may result from an inhibition of nitric oxide synthase (NOS), particularly inducible NOS (iNOS).