Background The efficacy of inhaled corticosteroids (ICS) varies among wheezing preschool children. Currently, it is not possible to predict which fraction of wheezing children will benefit from an ICS treatment. Objective We explored whether fractional exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC) can predict an ICS response in preschool wheezers. Methods An 8-week ICS study (registered at Clinicaltrial.gov: NCT 00422747; 200 mug; beclomethasone extra-fine daily) was performed in 93 wheezing children (age range 2.0-4.4 years). At baseline, FeNO was determined off-line. EBC was collected using a closed glass-condenser. The acidity of EBC was determined and other EBC markers [interleukin (IL)-1alpha, IL-2, IL-4, IL-5, IL-10, soluble intercellular adhesion molecule, interferon-gamma, eotaxin] were measured using a multiplex immunoassay. The change in airway resistance (Rint) and symptom score following ICS treatment was related to atopy (positive Phadiatop Infant test), FeNO and EBC markers. Results Airway resistance and symptoms mildly improved after ICS treatment [median (IQR): 1.4 (1.2-1.7) to 1.3 (1.1-1.5) kPa s/L, symptom score: 26 (23-28) to 28 (24-29), P<0.01, respectively]. Only IL-10 and atopy had limited predictive value regarding a change in symptoms [beta (SE)=-0.13 (0.07), P=0.08, beta (SE)=2.05 (1.17), P=0.08, respectively]. Conclusions and Clinical Relevance We did not find convincing evidence that FeNO and EBC markers could predict an ICS response in preschool wheezers. Recommendations for future studies on this topic are given.