We studied 113 patients with CF and compared their responsiveness to inhaled methacholine to that of 50 asthmatic children and 26 normal children. Positive responses to MCh occurred in 51% of the patients with CF and 98% of those with asthma. There was a significant correlation between a positive response to MCh in CF and poor pulmonary function. There was no relationship between allergic rhinitis or positive allergen skin tests and a positive MCh response. Dose-response curves and time course to MCh challenge differed in CF and asthma. Bronchial hyperreactivity is thus common in CF but is different from that in asthma.