Environmental tobacco smoke (ETS) exposure is one of the commonest pollutants in modern society. Despite documented clinical adverse effects of ETS on the lungs, objective methods of assessing airway damage have been lacking. Exhaled nitric oxide (eNO) is a rapid, sensitive method of assessing airway inflammation, and could be useful in this regard. Active smoking decreases eNO in normal subjects and eNO levels are low in habitual smokers, but the effect of ETS exposure on eNO has not previously been examined. In a single-blinded, placebo-controlled cross-over study, we examined the effect of ETS, sham and active smoke inhalation on eNO in non-smoking normal volunteers. Subjects were exposed to smoke over a period of 1 hour in a separately ventilated chamber, and eNO was measured at baseline, 15, 30, 45 and 60 minutes. With sham inhalation (n = 15), eNO levels did not change significantly from baseline, although a small decrease occurred. ETS exposure (n = 15) resulted in a rapid fall in eNO from mean (SE) 134 (29) ppb to 102 (22) ppb, or by 23.6% (p < 0.05), and remained low for 60 minutes. With active smoking (n = 7), levels fell acutely from baseline within the same time interval (71 [16] to 49 [11] ppb, or by 30.3%), and remained low. These changes were significant compared with sham exposure for both ETS (p < 0.05) and active smoke inhalation (p <.01). This suggests that eNO can be used for the investigation of the mechanisms of cigarette-induced lung damage in the experimental setting, and may potentially be useful also for environmental assessment of ETS effects.