The biophysical properties of purified native (nonreduced) mucus glycoproteins (mucins) isolated from lung mucus secretions of cystic fibrosis (CF) patients and subjects with normal lungs were studied using the technique of light scattering. The effects of different NaCl concentrations and 6 M guanidine hydrochloride on the molecular size of mucins, their ability to form aggregates, and their shape were investigated. Under the concentration range studied (0.05—3.5 mg/ml), in buffered 0.03 and 0.01 M NaCl, the CF mucins had higher molecular weights (12.2 X 10⁶ to 17.1 X 10⁶ and 9.5 X 10⁶ to 10.4 X 10⁶, respectively) than those observed in buffered 0.15 M NaCl (4.3 X 10⁶ to 6.6 X 10⁶). These results were interpreted in terms of CF mucins self-aggregating in buffered 0.03 and 0.01 M NaCl. In contrast, in both buffered 0.3 and 0.15 M NaCl, the normal respiratory mucins had molecular weights of 6.3 X 10⁶ to 8.6 X 10⁶, thus suggesting the absence of normal mucin aggregation in buffered 0.03 M NaCl. In the presence of 6 M guanidine HCl both CF and normal mucins had molecular weights of about 5 X 10⁶ and showed more extended structure (i.e., larger radius of gyration) than in the presence of 0.03 or 0.15 M NaCl. Studies of the relationship of the light scattering intensity with scattering angle showed that, under the above experimental conditions studied, both CF and normal respiratory mucins were polydisperse flexible coil-shaped molecules. The increased aggregation of CF mucins observed at lower salt concentrations may alter the viscoelastic properties of CF lung mucus secretions.