Dry powder mannitol has the potential to be used to enhance clearance of mucus in subjects with bronchiectasis. A reduction in FEV has been recorded in some subjects with bronchiectasis after inhaling mannitol. The aim of this study was to investigate if pre-medicating with either sodium cromoglycate (SCG) or eformoterol could inhibit this reduction in FEV. A double-blind, placebo-controlled, randomized cross-over study was conducted. Lung function and airway response to mannitol was assessed on a control day and then re-assessed after pre-medication with placebo, SCG and eformoterol in nine subjects. Sensitivity to mannitol, expressed as the dose required to induce a 15% fall in FEV (PD), and reactivity to mannitol, expressed as the % fall in FEV per mg of mannitol (response-dose ratio, RDR), are reported. Subjects had an FEV of 68 ± 14% predicted, FVC of 97 ± 15% predicted and FEV/FVC of 71 ± 8%. They were mildly hypoxemic and the SpO was 95 ± 2%.They had a PD to mannitol of 235 mg (95% CI: 150-368 mg) and a RDR of 0.057% fall in FEV per mg (95% CI: 0.038-0.085). After pre-medication with SCG, PD increased (773 mg, P < 0.05) and RDR was reduced (0.013, P < 0.05). Pre-medication with eformoterol also resulted in an increased PD (1141 mg, P < 0.01) and a reduced RDR (0.009, P < 0.01). A small but significant decrease in SpO from baseline was noted after mannitol in the presence of SCG ( P < 0.05). Pre-medication with either SCG or eformoterol protects patients with bronchiectasis from developing a significant reduction in FEV after inhaling mannitol. A reduction in FEV is recorded in a significant minority of patients with bronchiectasis following inhalation of mannitol. This study reports that pre-medication with a standard dose of either sodium cromoglycate or eformoterol can protect this patient group from developing mannitol induced bronchospasm.