Patients with symptoms suggestive of asthma often have normal resting pulmonary function. In these patients, a determination of airway responsiveness by bronchial challenge is useful in demonstrating bronchial hyperreactivity (BHR), a defining feature of asthma. In the methacholine (Mch) challenge, it is recommended that following a baseline measurement of FEV1, the patient inhale the normal saline (NS) diluent and FEV1 be repeated to assess for nonspecific BHR to NS. It is also recommended that post-NS inhalation FEV1 should be used as the control value from which decrement in FEV1 is compared following Mch challenge. Mch testing was performed in 44 patients with symptoms suggestive of asthma (cough, chest tightness, dyspnea) and normal resting pulmonary function. Baseline spirometry was obtained and repeated after inhalation of NS and after five breaths each of Mch at the following concentrations: 0.025 mg/ml, 0.25 mg/ml, 2.5 mg/ml, 10 mg/ml, and 25 mg/ml. The procedure was terminated when FEV1 decreased to at least 80% of the post-NS value or if the maximal concentration of Mch had been reached. The post-NS FEV1 value was > or = 91% of the pre-NS value in all the subjects range 91-105%). Using the post-NS FEV1 as the recommended control value, 20 patients (45%) had a positive Mch challenge and 24 patients (55%) had a negative Mch challenge. Had we used the pre-NS FEV1 as a control value, only 2 patients would have been reclassified, and when these 2 cases are carefully examined, there would have been no significant change in the clinical interpretation of the MCh test.(ABSTRACT TRUNCATED AT 250 WORDS)