Methacholine inhalation challenge (MIC) is probably the most widely used and best standardized test for nonspecific bronchoprovocation challenge (BPC). There has been increasing interest in developing "physical" stimuli such as eucapnic voluntary hyperventilation (EVH) with dry gas to assess airway hyperreactivity (AHR), because of inherent problems with using a pharmacologic agent in epidemiologic surveys. To our knowledge, no studies exist that compare MIC with EVH in known asthmatics. We conducted a prospective, randomized, crossover trial with a group of subjects (n = 16) who met the American Thoracic Society definition of asthma with these objectives: (1) to compare the sensitivity of EVH with MIC; (2) to compare the quantitative response of one test with the response to the other challenge; and (3) to correlate the response of both tests with symptoms, serum IgE levels, and serum eosinophil counts. We found that (1) EVH was positive in 75 percent of cases and MIC was positive in 81 percent of cases; one subject reacted to EVH but not to MIC and vice-versa. (2) The quantitative response to one test correlated with the response to the other test (r = -0.60, p = 0.01). (3) There was a correlation between severity of asthma symptoms and the response to EVH (r = 0.62; p = 0.01), but not to MIC. (4) Response to MIC (log PD20), but not EVH, correlated with serum IgE level (r = -0.53, p = 0.04). We suggest that EVH may be used for the initial assessment of AHR in the evaluation of asthma. Eucapnic voluntary hyperventilation is a sensitive measure of AHR and it correlates well with symptoms. Furthermore, though these points were not addressed in our study, it is more physiologic than MIC, and it is easy and less expensive to perform.