STUDY OBJECTIVES: It has been demonstrated previously that exhaled nitric oxide (eNO) is increased in steroid-naive asthmatics and that inhaled steroids reduce eNO in these patients. Cigarette smoking has also been reported to reduce the eNO in healthy volunteers. Recently a correlation has been demonstrated between eNO and airway hyperresponsiveness in steroid-naive, mild asthmatics. We hypothesized that cigarette smoking would reduce the eNO level in steroid-naive asthmatics and might, therefore, affect the correlation between eNO and airway hyperresponsiveness. DESIGN: Comparison of eNO in healthy smoking and nonsmoking volunteers with the level of eNO in steroid-naive and steroid-treated asthmatics. Correlate the eNO level with the provocative concentration of histamine causing a 20% fall in FEV1 (PC20hist) in the asthmatic smoking and nonsmoking patients. SETTING: University outpatient asthma clinic. PATIENTS AND METHODS: eNO levels and PC20hist were measured in three different asthmatic patient groups (group A = 29 steroid-naive, nonsmoking asthmatics; group B = 19 steroid-treated, nonsmoking asthmatics; and group C = 13 smoking, steroid-naive asthmatics) and in two healthy volunteer groups (group D = 18 nonsmoking; and group E = 16 smoking). RESULTS: eNO in group A was significantly increased compared with the values in groups B and D (21.8+/-12.7, 12.8+/-4.9, and 10.6+/-2.2 parts per billion [ppb], respectively). Cigarette smoking decreased eNO in healthy volunteers (7.4+/-1.8 ppb, group E) as well as in steroid-naive asthmatics (12.7+/-5.1 ppb, group C). There was a significant correlation between eNO and PC20hist in group A (r = -0.45, p < 0.05); this correlation was, however, lost in both groups B and C. CONCLUSION: Cigarette smoking and inhaled steroids reduce the eNO in patients with mild asthma to a comparable extent. Because the correlation between eNO and airway hyperresponsiveness was lost in steroid-treated and smoking, steroid-naive asthmatics, we question the value of eNO as a marker of airway inflammation, at least in mild asthmatics who are already being treated with inhaled steroids or who are currently smoking.