The binding of antibiotics to macromolecules isolated from patients with chronic bronchitis may result in decreased efficacy due to a reduction in the active form of the drug, although this phenomenon has received little attention until now. Cefuroxime axetil is an oral cephalosporine proposed for the treatment of exacerbations of chronic bronchitis. We describe a high-performance liquid chromatography-based method for determining the concentration of cefuroxime bound to soluble macromolecules in bronchial mucus. Using this technique we found that the "in-vitro" binding of cefuroxime to soluble macromolecules of the bronchial mucus was low; the large "free" fraction (70 %) may partly account for the clinical efficacy of cefuroxime axetil in the treatment of superinfected chronic bronchitis.