There is considerable dispute regarding the prevalence of asthma in patients with cystic fibrosis (CF). We studied 50 patients with CF and compared their responsiveness to inhaled histamine with that of asthmatic children. The incidence of positive responses to inhaled histamine was 24% in the patients with CF and more than 90% in the asthmatic patients. We found no correlation, in the patients with CF, between the histamine response and several indexes of atopy (clinical allergic disease and positive allergen skin tests). Positive responders to histamine were not evenly distributed over the disease spectrum of CF. Instead, positive responses occurred only in those patients whose prechallenge pulmonary function was abnormal. We conclude that the heightened bronchial reactivity in patients with CF reflects the severity of their underlying lung disease rather than the presence of coexistent asthma.