In the search for markers of airway inflammation, we investigated the role of soluble interleukin-6 receptor (sIL-6R) in patients with bronchial asthma. Serum levels of sIL-6R were measured in 20 patients with stable asthma and in 18 healthy control subjects by means of a sandwich enzyme-linked immunosorbent assay. Such levels were also evaluated during a spontaneous attack of asthma (n = 10) as well as that after allergen inhalation (n = 7). Results were compared with those observed during the stable state and after the inhalation of methacholine. Serum levels of sIL-6R in asthmatic patients (132 +/- 31 ng/ml) significantly exceeded those of control subjects (111 +/- 16 ng/ml) (p < 0.05). These levels showed no correlation with such clinical variables as nonspecific bronchial hyperreactivity, atopic status, or serum concentration of IgE. Serum sIL-6R levels observed during an asthmatic attack versus those during the stable state (4 wk later) differed significantly. After a severe attack of asthma, such levels were significantly elevated on the second and third days, but not on Day 5. After challenge, circulating levels of sIL-6R were significantly increased 24 h after the inhalation of allergen but not of methacholine. Results suggest that serum levels of sIL-6R are increased in patients with asthma and are further increased during a spontaneous attack or that provoked by the inhalation of allergen. Thus, serum sIL-6R may reflect inflammation of the airway. Further studies are indicated to determine the clinical significance and the application of serum levels of sIL-6R in evaluating asthmatic patients.