Cyclooxygenase products modulate the expression of nitric oxide synthase (NOS) in certain cell types. We determined the effect of prostaglandins (PG) E2 and F2 α on exhaled nitric oxide (NO) concentrations measured by chemiluminescence. Inhaled PGE2 and PGF2 α significantly reduced exhaled NO. After the highest dose of PGE2 (100 μg), 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 PGF2 α, 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 PGF2 α 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 PGF2 α 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).