Increased serum and sputum concentrations of eosinophil cationic protein (ECP) and of neutrophil myeloperoxidase (MPO) have been described in patients with cystic fibrosis. Because numbers of eosinophils are normal in both peripheral blood and in the lung of patients with cystic fibrosis, we investigated whether eosinophils presented with an increased propensity to release their granule proteins. We investigated 20 patients with cystic fibrosis, 19 individuals with bronchial asthma, and 21 healthy nonatopic subjects. Isolated granulocytes were stimulated with serum-opsonized Sephadex G15 particles and the released amounts of ECP and MPO were measured by using radioimmunoassays. Eosinophils of patients with cystic fibrosis released significantly higher amounts of ECP than control subjects (p < 0.0001) and individuals with bronchial asthma (p < 0.0001). The release of MPO from neutrophils was also higher (p < 0.0001 and p < 0.005, respectively). Furthermore, a significant relationship between clinical variables and secretory activity of eosinophils was found in cystic fibrosis. We conclude that eosinophils as well as neutrophils obtained from patients with cystic fibrosis have an increased propensity to release their granule proteins which may be due to priming mechanisms. These findings would support anti-inflammatory treatment modalities in cystic fibrosis.