Conventionally, symptoms occurring during the methacholine test are not taken into account when interpreting the test results. We examined whether the evaluation of methacholine-induced symptoms (MIS) added to the test interpretation based on the PC20FEV1 by assessing their prevalence, their similarity with symptoms justifying referral and their relationship with airway responsiveness. Eighty-two patients with suspected asthma completed a questionnaire of symptoms and underwent bronchial challenge with methacholine. Based on MIS and airway responsiveness (responders = PC20FEV1 < 8 mg/mL), subjects were classified as asymptomatic non-responders (ANRs), asymptomatic responders (ARs), symptomatic non-responders (SNRs) and symptomatic responders (SRs). Airway responsiveness for all subjects, including non-responders (ie, fall in FEV1 < 20%), was assessed by the methacholine concentration response-slope (MCRS) obtained using all points of the curve. ARs (n = 6) were poor-perceivers of bronchoconstriction. SNRs (n = 16) did not differ from SRs (n = 34) in any clinical parameter, including the proportion of subjects (∼80%) whose methacholine test reproduced symptoms justifying referral. In turn, SNRs differed significantly from ANRs (n = 26) by having lower baseline FEV1 (P = .005), more physician-diagnosed asthma (P < .001), more use of respiratory medication (P = .032), and relatively greater responsiveness as manifested by a steeper MCRS (P < .001). The occurrence of asthma-like symptoms during the methacholine test was associated with milder airway hyperresponsiveness that would go unnoticed by the PC20FEV1. This finding suggests that SNRs should not be merely classified as having normal responsiveness, as currently recommended, but further assessed for airway inflammation. Our results helped planning a longitudinal study to investigate the prognostic validity of this approach. © 2017 John Wiley & Sons Ltd.