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BACKGROUND: There are no predictors known that can identify COPD patients who will respond to treatment with ICS. METHOD: We investigated 30 patients (median age 65 (range 44-83, 12 females) with mild to moderately severe COPD. All patients had post bronchodilator FEV1/forced vital capacity ratio of less than 70% and a reversibility of less than 12% and 200 ml from baseline. We wanted to determine if airway responsiveness (AHR) to histamine and mannitol could predict who would respond to a 3-month course of ICS. RESULTS: At baseline, all patients had AHR to histamine, but only 7 (23%) patients to mannitol. After 3 months of treatment with ICS, there was no significant change in spirometry or the quality of life when analysing all individuals together. However, FEV1% predicted improved from 67% (IQR12) to 79% (IQR16) in mannitol positive patients; whereas it was unchanged in the mannitol negative patients. The difference in the mean change of FEV1% predicted between the two groups was 12 (IQR13.5) and this was highly significant (p=0.001). The improvement in quality of life (SGRQ 30 (IQR10.5) to 21 (IQR12; p=0.01) was only significant in the patients positive to mannitol. CONCLUSION: We propose that AHR to mannitol could predict ICS-responsiveness in mild to moderately severe COPD patients.