To evaluate whether concentrations of cytokines supposed to be involved in eosinophil recruitment and activation were elevated in cystic fibrosis (CF), we assessed interleukin-3 (IL-3), IL-5, IL-8, regulated on activation, normal T-cell expressed and secreted (RANTES); and granulocyte-macrophage colony stimulating factor (GM-CSF) in sputa from 32 patients with CF, eight patients with atopic bronchial asthma, and six patients with bacterial pneumonia. In addition, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as markers of eosinophil activation. In patients with CF, sputum levels of IL-8 were elevated (p < 0.01) as compared with asthmatic patients. Concentrations of IL-3, ECP, and EPX were not different in the two groups. However, IL-5 (p < 0.0001), RANTES (p < 0.003), and GM-CSF (p < 0.0001) were significantly lower in the CF group than in subjects with asthma. IL-5 was detected only in sputum samples from CF patients with Aspergillus sensitization. In patients with pneumonia, IL-8 levels only were increased. In CF sputum, ECP levels were significantly correlated with the levels of IL-8 (r = 0.626, p < 0.0001) and IL-3 (r = 0.642; p < 0.0001), whereas in asthmatic patients IL-5, IL-8, and RANTES concentrations were significantly related to ECP in sputum. These findings suggest that different cytokine profiles are responsible for eosinophil activation in patients with CF as compared with asthmatic patients. In CF, IL-8 and IL-3 appear to be responsible for increased degranulation of eosinophils.