We compared the responses to inhaled methacholine, ultrasonically nebulized distilled water, and exercise in 25 subjects with atopic asthma. The methacholine inhalation test and challenges with distilled water and exercise were performed on three separate days 48 hours apart. Bronchial responsiveness to methacholine and ultrasonically nebulized distilled water was measured as the concentration of methacholine (PC20M) and the volume output of the ultrasonic nebulizer (PO20 UNDW) producing a 20 percent fall in the forced expiratory volume in one second (FEV1). The response to exercise was expressed as the percentage of fall in FEV1 from the value before exercise. Seventeen subjects showed a fall in FEV1 of more than 20 percent after exercise. Eight subjects had a stimulus-response curve to distilled water that was flat up to the maximal volume output from the nebulizer, but only four of them also showed no significant response to exercise. The response to exercise correlated better with PO20 UNDW (r = -0.66; p less than 0.01) than with PC20M (r = -0.19; p greater than 0.5) in those responding to distilled water. In all of the tested subjects, exercise-induced bronchoconstriction correlated with PC20M (r = -0.61; p less than 0.01). The mean PC20M was significantly lower in the subjects with a significant response to distilled water and exercise (p less than 0.001 and p less than 0.0001, respectively). We concluded that ultrasonically nebulized distilled water and exercise provoke significant bronchoconstriction in the subjects with more severe nonspecific bronchial hyperresponsiveness. The correlation found between the two stimuli supports the hypothesis that they act by similar mechanisms.