Management plans for childhood asthma show limited success in optimising asthma control. The aim of the present study was to assess whether a treatment strategy guided by airway hyperresponsiveness (AHR) increased the number of symptom-free days and improved lung function in asthmatic children, compared with a symptom-driven reference strategy. In a multicentre, double-blind, parallel-group, randomised, 2-yr intervention trial, 210 children (aged 6-16 yrs) with moderate atopic asthma, selected on the basis of symptom scores and/or the presence of AHR, were studied. At 3-monthly visits, symptom scores, forced expiratory volume in one second (FEV(1)) and methacholine challenge results were obtained, and medication (five levels of fluticasone with or without salmeterol) adjusted according to algorithms based on symptom score (reference strategy, n = 104) or AHR and symptom score (AHR strategy, n = 102). After 2 yrs, no difference was found in the percentage of symptom-free days between treatment strategies. Pre-bronchodilator FEV(1) was higher in the AHR strategy (2.3% predicted). This was entirely explained by a gradual worsening of FEV(1) in a subgroup of 91 hyperresponsive children enrolled with low symptom scores (final difference between study arms was 6%). Asthma treatment guided by airway hyperresponsiveness showed no benefits in terms of number of symptom-free days, but produced a better outcome in terms of pre-bronchodilator forced expiratory volume in one second in allergic asthmatic children, especially those characterised by low symptom scores despite airway hyperresponsiveness.