The interaction of secretory leucocyte proteinase inhibitor with bronchial mucins and glycopeptides was studied by means of c.d. spectroscopy. The interaction with mucins was characterized by an increase in organized structure of alpha-helical type, as evidenced by the appearance in the difference spectra of two positive bands at 208 and 218 nm. This phenomenon was correlated with the amount of inhibitor present in the mixtures, suggesting that the change was inherent to the inhibitor. Surprisingly, when the inhibitor was mixed with acid glycopeptides, difference c.d. spectra showed a decrease in organized structure, characterized by a negative minimum at 196 nm. Glycopeptides treated with neuraminidase gave similar profiles of difference spectra in three different mixtures, indicating that the interaction was smaller. The interaction between the inhibitor and mucins was also studied for its ability to modify in vitro the proteolytic activity of human leucocyte elastase. Mucins alone were degraded by that proteinase into glycopeptides of Mr 400,000-500,000, whereas mucins mixed with inhibitor before adding elastase were proteolysed to a lesser extent. These data demonstrate that the secretory leucocyte proteinase inhibitor interacts with mucins and consequently is capable of protecting the mucins against proteolysis by elastase.