Background and objective: Exercise-induced wheeze (EIW) is common. Several treatment options exist. Patients with low fraction of exhaled nitric oxide (FNO) are unlikely to be steroid-responsive and might benefit from non-steroidal therapies. We assessed: the efficacy of cromoglycate, formoterol and montelukast in patients with EIW and low FNO (35 ppb) group. Methods: Patients had EIW and airway hyperresponsiveness (AHR) to mannitol and/or exercise. Those with low F NO (n = 19) received cromoglycate (20 mg inh. bd + before challenge tests), formoterol (12 μg inh. bd + before challenge tests) and montelukast (10 mg p.o. od), each for 2 weeks. Those with high FNO (n = 20) took inhaled fluticasone (500 μg) daily for 4 weeks. Primary end-points were: 50% reduction in maximum FEV %fall (clinical protection) and decrease in AHR to mannitol. Results: In patients with low FNO, cromoglycate, formoterol and montelukast significantly decreased AHR to mannitol in 63%, 61% and 47% of patients, respectively. In this group, the magnitude of exercise-induced bronchoconstriction (EIB) was significantly reduced with montelukast and formoterol; between-treatment differences were not significant. Of 6/19 with low FNO and EIB, protection occurred in 67% (cromoglycate), 83% (formoterol) and 50% (montelukast), respectively. In the high FNO group, AHR to mannitol and EIB decreased significantly with fluticasone (P <0.001, P = 0.005, respectively), and protection occurred in 7/8 (88%) with EIB. Conclusions: In patients with EIW and low FNO, the number of 'responders' to cromoglycate, formoterol and montelukast was similar. In a high FNO population the response to inhaled corticosteroid was highly significant and comparable to previous studies.