Bronchial hyperreactivity is a characteristic feature of asthma and can be evaluated by different challenges. The aim of this study was to compare exercise, methacholine (MCH), and adenosine 5'-monophosphate (AMP) challenges in 135 children and young adults (mean age +/- SD, 12.4+/-3.9 years) with asthma, and to examine the utility of the different challenges in predicting those children with asthma likely to require prophylactic antiinflammatory treatment. The sensitivity of MCH challenge in detecting bronchial hyperreactivity (at or below 8 mg/mL) was 98%, that of AMP challenge (at or below 200 mg/mL) 95.5%, and that of exercise (more than 8.2% fall in FEV(1)) was 65%. There was a significant difference between mild asthmatic children (85 patients, intermittent asthma, step 1 of NIH guidelines) and moderate asthmatics (50 patients, steps 2 and 3 of guidelines) in relation to the logarithmic mean provocation concentration to elicit a 20% fall in FEV(1) (PC(20)) to MCH (0.49 mg/mL vs. 0.15 mg/mL, P<0.00001), that to AMP (7.67 mg/mL vs. 3.60 mg/mL, P = 0.001), and in relation to the mean percent fall in FEV(1) after exercise (13.9% vs. 22.0%, P = 0.001). Sensitivity and specificity curves between the two severity groups of asthma were constructed, and the intersection point of the two curves for each type of challenge was determined. When mild asthmatics were compared to moderate asthmatics, the intersection points for MCH, AMP, and exercise were 66%, 63%, and 61%, respectively. Logistic regression analysis and receiver operating characteristic (ROC) curves of the three challenges for the two severity groups of asthma showed that methacholine was a better discriminating challenge between the severity groups than the other two challenges. We conclude that the sensitivities of AMP and MCH challenges in the detection of bronchial hyperreactivity in children and young adults with asthma are very similar and higher than that of exercise. There is a significant difference between mild and moderate asthmatics within the three bronchial challenges, with MCH discriminating better than AMP or exercise between groups.