Chronic airway inflammation is a hallmark of cystic fibrosis (CF). Biological products with chemotactic activity are essential for neutrophil recruitment to sites of inflammation. The presence of a factor with chemotactic activity higher than that of interleukin (IL)-8 in the bronchial secretions of patients with CF has recently been reported. This article reports that the chemotactic activity of this factor remained unaffected by a variety of physical treatments and could be distinguished from those of IL-8, formylmethionylleucylphenylalanine, leukotreine B4, and platelet-activating factor. The factor induced chemotaxis and chemokinesis locomotion of neutrophils, and its chemotactic activity was sensitive to pertussis toxin and thapsigargin. Semipurified preparation of the chemotactic factor increased transiently intracellular Ca(2+) concentration but failed to stimulate the release of neutrophil primary granules and the production of superoxide, suggesting that the semipurified chemotactic factor is a Ca(2+)-dependent chemoattractant of neutrophils, acting via pertussin toxin-sensitive G protein-coupled surface receptors, that directs neutrophil movement toward the airway epithelium.