To study wheeze as an indicator of bronchial responses during standardized methacholine challenge (MCH), we used computerized analysis of respiratory sounds in children with cystic fibrosis (CF) and in healthy control subjects. We recorded tracheal and lung sounds from 10 young CF = yCF patients, mean age 5.7 yr (range 4 to 7 yr), 13 older CF = oCF, age 10.5 yr (8 to 18 yr), 7 young normal subjects = yNO, age 5.3 yr (4 to 7 yr), and 11 older normal subjects = oNO, age 11 yr (8 to 16 yr). Spirometry was obtained after each doubling concentration of methacholine until the concentration provoking a > or = 20% fall in FEV1 (PC20) or the end point (8 mg/ml) was reached. Sound and calibrated flow signals were recorded on tape and later analyzed by respirosonography. The concentration of methacholine associated with wheeze (PCw) was noted. Wheezing was quantified by its duration during inspiration (Tw/TI) and expiration (TW/TE). We found a positive response to MCH in 11 of 13 oCF (PC20 0.75 mg/ml, range 0.08 to 3.0) and in 3 of 11 oNO (PC20 4.2 mg/ml, range 2.5 to 6.5). Wheezing occurred in 6 oCF (PC20 < 8 mg/ml). In 7 yCF PC20 or PCW developed (1.51 mg/ml, range 0.125 to 4.0) versus 4 yNO (4.0 mg/ml, range 2.0 to 8.0). In 10 oCF subjects who performed MCH on three occasions within a 2-wk period, both positive and negative wheeze responses were reproducible. Patients who wheezed had a lower FRC compared with patients who did not (109 versus 147% of predicted, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)