We studied 20 children with cystic fibrosis who had relatively normal pulmonary function (forced expiratory volume greater than or equal to 70% of predicted) to determine whether demonstration of heightened bronchial reactivity in this group reflects coexistent asthma. Using a standardized histamine provocation, we found that eight (40%) had a positive response. These responders were significantly younger than the nonresponders, had a greater incidence of clinical asthma, and all were atopic on skin testing. However, they had a significantly higher ratio of residual volume to total lung capacity than the nonresponders. Although as a group they were less sensitive to histamine than children with asthma, four of the responders with cystic fibrosis had histamine sensitivity similar to a group of asthmatic patients. We concluded that, in the presence of mild lung disease, the demonstration of heightened bronchial reactivity in children with cystic fibrosis may provide confirmatory evidence of coexistent asthma, particularly if the children are highly sensitive to histamine.