Assessment of exhaled nitric oxide (eNO) in patients with chronic obstructive pulmonary disease (COPD) provides seemingly conflicting results and the relationships between eNO and other sputum inflammatory mediators are relatively weakly recognized. In the present study we measured eNO in 63 subjects (14 non-smoking healthy controls and 49 COPD stable patients--15 patients at stage 0, 9 patients at stage 1, 16 patients at stage 2, and 9 patients at stage 3). Additionally, concentrations of cytokines (IL-8, TNF-alpha, TGF-beta1, GM-CSF, Eotaxin) and nitrogen oxides (as nitrite or nitrate) (NOs) were measured in induced sputum in these patients. We found that there were no significant differences between the means of either eNO or NOs levels in COPD patients (stage 0-2) and controls. The only significant difference was noted for NOs between the COPD stage 3 patients and controls (9.0+/-1.7 microM vs. 21.1+/-4.8 microM). There was no significant correlation between eNO and sputum NOs. No relationships existed between eNO and the examined cytokine levels, except for a single negative correlation with GM-CSF (r=-0.38, P=0.02). In contrast, NOs correlated positively with IL-8 levels (r=0.51, P<0.01) and IL-8 levels correlated negatively (r=-0.47, P<0.01) with FEV1. We conclude that exhaled NO, sputum NOs, and other sputum cytokines offer separate and additive information about the pathophysiological condition in COPD.