Measurement of bronchial airway responsiveness requires noninvasive techniques in young children. The study was designed to examine the changes in resistance as measured using the interrupter technique (Rint) at the dose of methacholine (M) that induced a fall in transcutaneous partial pressure in O-2 (PtcO2) greater than or equal to 20% (PD20PtcO2) in young children. Rint was calculated using the linear back-extrapolation method (Rint(L)) and the end-interrupter method (Rint(El)). Twenty-two children (mean age, 5.2 +/- 1.1 years; range, 3.4 - 7.1 years) with nonspecific respiratory symptoms (mainly chronic cough, n = 17) were tested, PtcO2, Rint(L), and Rint(El) were measured before the test, after saline challenge (baseline (B)), after each dose of M delivered by a dosimeter, and after bronchodilator (BD) inhalation. PtcO2 decreased significantly during M challenge, from 85+/-6 mmHg (B) to 62+/-9 mmHg (P<0.05), and increased after ED inhalation, to 82+/-8 mmHg. Rint(L) and Rint(El) increased significantly during M challenge, from 0.94+/-0.2 KPa/L/s and 1.11+/-0.19 KPa/L/s (B) to 1.27+/-0.35 KPa/L/s and 1.47+/-0.37 KPa/L/s, respectively (P<0.05), and decreased after ED inhalation to 0.80+/-0.17 KPa/L/s and 0.95+/-0.18 KPa/L/s, respectively. Nineteen of 22 children reached the PD20PtcO2 at a dose of M ranging from 50-400 mug At the PD20PtcO2, significant changes in Rint(L) and Rint(El) (sensitivity index (SI)greater than or equal to 2) were found in 79% and 63% of children, respectively. We conclude that: 1) M challenge using PtcO2 is safe in young children; and 2) our findings are not in favor of the use of Rint as the only indicator of bronchial reaction in young children during M challenge.