The mechanisms by which immunotherapy (IT) modulates allergic airway response are not entirely clear. Exhaled nitric oxide (eNO) is a sensitive marker of airway inflammation in allergic respiratory disorders. We hypothesize that eNO may serve as a barometer of the immunomodulatory changes occurring during IT. We aimed to characterize the pattern of eNO levels in children undergoing traditional IT (TradIT) and rush IT (RushIT). Off-line measurements of eNO were obtained in children electing to undergo RushIT or TradIT at a University-based Allergy/Asthma Clinic. The eNO was measured before IT (pre-IT, week 0) was initiated, and at 2, 4, 6, 8, and 12 weeks after starting IT. Nine children received TradIT and 10 children received RushIT. Pre-IT eNO in the RushIT group averaged 12.6 parts per billion (ppb). This was followed by a rise to 17.7 ppb at week 2. The elevated eNO levels persisted till week 8, and then dramatically dropped below the pre-IT values to 8.9 ppb at week 12 (p = 0.038). Similar changes in eNO were not seen in the TradIT group. The difference in eNO levels between the two groups was most marked at 4 weeks (p = 0.014). Initiation of IT produces significant immunomodulatory changes such as a rise in eNO levels. Temporally, the changes appear to be accelerated in the RushIT group compared with the TradIT group, with return to baseline as maintenance IT levels are achieved.