The authors compared the inhaled methacholine and exercise responses in 22 stable unmedicated asthmatic patients. The exercise and methacholine challenges were performed at one to three week intervals. Bronchial responsiveness to methacholine was measured in relation to the concentration of methacholine (PC20M). The response to exercise was expressed as the percentage of fall in FEV1 from the pre-exercise FEV1. The findings showed that 21 of 22 subjects demonstrated a fall in FEV1 of more than 20% after methacholine challenge, while only 9/22 subjects experienced a similar decrease in FEV1. All 9 of these positive response exercise cases completed three consecutive exercise challenges prior to the methacholine challenge. Of these cases, five were refractory to the repeated exercise challenge, and the PD20M at the nonexercise stage was significantly lower than the postexercise state. In fact, the methacholine challenge sensitivity actually decreased (PD20 increased) after repeated exercise. The authors concluded that methacholine seems to be a more sensitive bronchial provocation test than exercise. Second, only 55.6% of the exercise test-positive subjects were refractory to the second exercise challenge. Therefore, other factors besides the release of mediators should be considered in exercise-induced asthma. Third, methacholine sensitivity actually decreased (PD20 increases) after repeat exercise challenge.