We have previously demonstrated that normal healthy infants exhibit airway reactivity to inhaled methacholine. The purpose of this study was to evaluate the changes in airway reactivity with age in infants and young children. We tested 24 healthy term subjects 4 to 24 months of age (mean 13 months) with history negative for lower respiratory illnesses and wheezing. Airway function was assessed by maximal expiratory flow at FRC (VmaxFRC), generated by rapid chest compression. After baseline measurements, each subject inhaled increasing concentrations of methacholine (Mch), beginning with 0.075 mg/ml, until VmaxFRC decreased 30% or Mch = 2.5 mg/ml. Sensitivity to Mch was defined as the threshold concentration (TC) required to decrease VmaxFRC 2 SD from control, and the Mch required to decrease VmaxFRC 30% (PC-30). Airway reactivity was defined as the slope between TC and PC-30 (SPC-30). We found significant regressions for TC, PC-30, and log SPC-30 versus age. TC and PC-30 increased with increasing age (r = 0.51, p less than 0.02; r = 0.63, p less than 0.001, respectively), indicating decreasing sensitivity to Mch with increasing age. Log SPC-30 became less steep with increasing age (r = -0.59, p less than 0.01), reflecting decreasing reactivity to Mch with increasing age. Of these infants, 10 had their Mch challenge repeated a mean of 8 months (range 4 to 11.5) following their initial test, with no lower respiratory illnesses in the interim.(ABSTRACT TRUNCATED AT 250 WORDS)