To assess whether the peripheral airways are involved in pediatric asthma, 10 asthmatic children (aged 8-15 years), hyperresponsive to dry-air hyperventilation challenge (DACh), performed spirometry and a vital capacity He/SF(6) single-breath washout test at rest, after DACh, and after beta(2)-therapy. The normalized phase III slopes (Sn(III)) of the expired He and SF(6) concentrations served as measures of overall ventilation inhomogeneity, and the (SF(6) - He) Sn(III) difference served to indicate where along the peripheral airways obstruction occurs. While a greater increase in the He vs. SF(6) slope indicates that obstruction has occurred in the vicinity of the acinar entrance, the reverse suggests obstruction deeper in the intraacinar airways. The mean (SD) fall in FEV(1) after DACh was 35 (14)%. Both He and SF(6) Sn(III) increased significantly (P < 0.05) after the challenge, and were restituted after beta(2)-therapy (P < 0.05). After DACh, Sn(III) increased more for He than for SF(6), resulting in a negative (SF(6) - He) Sn(III) difference (P < 0.01), which was restituted after beta(2)-therapy (P < 0.05). Even though there was no correlation between baseline FEV(1) and the magnitude of the subsequent fall in this parameter after DACh (r(2) = 0.04; n.s.), a strong correlation was found between the (SF(6) - He) Sn(III) difference at rest and its change after DACh (r(2) = 0.81; P < 0.001). We conclude that airways close to the acinar entrance participate in the airway response to DACh in asthmatic children. The magnitude of this peripheral airway response is related to the severity of resting peripheral airway dysfunction.