The aim of the study was to assess feasibility, sensitivity, specificity, predictive value, and repeatability of cold, dry air challenge (CACh) as a diagnostic test for asthma in young children 2 to 5 yr of age. Response to a 4-min single-step isocapnic CACh was measured in 38 asthmatics and 29 control subjects. Specific airway resistance (sRaw) by whole body plethysmography was the primary outcome. In addition, lung function was measured as respiratory resistance by the interrupter technique (Rint) and respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique. At baseline, lung function measures differed significantly between asthmatics and healthy control subjects. CACh was readily performed in young children. Response was expressed as change from baseline in numbers of within-subject standard deviation (SDw). Hyperresponsiveness defined as change in lung function of more than 3 SDw was detected by sRaw in 26 of 38 asthmatics versus 2 of 29 control subjects, by Rint in 12 of 38 asthmatics versus 1 of 29 control subjects, by Xrs5 in 9 of 38 asthmatics versus zero of 29 control subjects and by Rrs5 in 7 of 38 asthmatics versus 1 of 29 control subjects. Thus sRaw had the highest sensitivity (68%). Specificity ranged from 93 to 100%. The correlation coefficient between sRaw responses to CACh repeated within 8 wk was 96%. In conclusion, CACh is feasible in young children age 2 to 5 yr. Whole body plethysmography (sRaw) was superior in separating asthmatics from healthy control subjects. Change in sRaw in response to CACh may be used as a diagnostic test for asthma in young children.