The majority of patients with cystic fibrosis (CF) become colonized with Aspergillus fumigatus (A. fumigatus) in the lower respiratory tract, the prevalence being up to 60%. Between 1-11% of CF patients develop allergic bronchopulmonary aspergillosis (ABPA). Previous studies of ABPA in selected patients suffering from cystic fibrosis or atopic asthma have suggested a pathogenic role for antigen-specific "Th2-like" T lymphocytes. The aim of this study was to evaluate the quantitative importance of such Th2 cells, using improved techniques for measuring interleukin-4 (IL-4) and IL-5 secretion in unseparated peripheral blood mononuclear cell (PBMC) suspensions from CF patients with ABPA and from a control group without ABPA. Thus, 20 patients with CF, heavily colonized with A. fumigatus in the lower respiratory tract, were studied: 10 patients with ABPA, and 10 without. Unseparated PBMC were stimulated in vitro by A. fumigatus antigen and by an unrelated antigen (tetanus toxoid) as a control. After 6 days of stimulation, IL-4 and IL-5 (markers for Th2 cell activity) and interferon-gamma (IFN-gamma) (marker for Th1 cell activity) were quantified in the supernatants by enzyme-linked immunosorbent assay. PBMC from ABPA patients secreted significantly higher amounts of IL-4, i.e., 0.48 (0.15-0.8) ng/mL (median (range)), and IL-5, 37.64 (0.32-82.85) ng/mL, compared to secretions obtained in non-ABPA CF controls of 0.07 (0.04-0.16) ng/mL and 3.00 (0.10-5.09) ng/mL, respectively (P < 0.01 for both). IFN-gamma secretion was similar in the two groups, amounting to 21.5 (2.05-72.5) ng/mL in ABPA patients vs. 20.75 (1.80-54.0) ng/mL in non-ABPA patients (P = 0.47). No significant differences were obtained in the cytokine secretion induced by tetanus toxoid stimulation between the two groups. We conclude that ABPA in CF patients is associated with an antigen-specific, Th2-like T-cell immune response, as indicated by excessive secretion of IL-4 and IL-5.