Tidal fractional exhaled nitric oxide (FE(NO)) changes were investigated in healthy, unsedated infants with or without prenatal tobacco exposure. Tidal flow (V), FE(NO), and CO(2) were measured in 20 healthy, unsedated infants [age: 25-58 days, length: 56.5 +/- 2.5 (SE) cm]. NO output (VNO) was calculated (VNO = FE(NO) x V). Two approaches were used to investigate within-breath changes of FE(NO) and VNO. First, we identified phases II and III from the expiratory capnogram. Second, we divided expiration into time-based quartiles. Tidal FE(NO) (range: 14.5 +/- 1.6 to 17.6 +/- 2.1 parts/billion: quartile 4 and phase II, respectively) was not different between portions and exhibited significant negative V dependence. VNO was significantly dependent on the expiratory portion, with quartile 4 being significantly lower than the remaining expiratory portions. Infants exposed to prenatal cigarette smoke (n = 7) exhibited significantly lower FE(NO) and VNO compared with nonexposed (n = 13) infants. We conclude that tidal FE(NO) is V dependent and that VNO may be a more suitable outcome parameter in variable V conditions. Prenatal tobacco exposure resulted in a decreased FE(NO) and VNO in infants.