In sputa of 21 cystic fibrosis patients suffering from chronic Pseudomonas aeruginosa lung infections, activities of lysosomal proteases released from polymorphonuclear leukocytes (PMN) and immune complexes were quantitatively determined. The results showed that low immune complex values correlated with high protease activities and vice versa. In a longitudinal study fluctuating, reciprocal changes of the parameters were observed. Therefore, the hypothesis was investigated as to whether PMN elastase cleaves immune complexes and regulates inflammation. It was shown that treatment of immune complex-positive sputa with PMN elastase decreased IgG and IgA immune complex values and lead to cleavage of the immunoglobulins in the hinge region. PMN elastase-treated samples were not able to stimulate the oxidative burst of PMN. Cleavage of in vitro built immune complexes did not lead to liberation of bound antigen. Western blot analysis of one sputum sample revealed split products of the IgG heavy chain. The results suggest that PMN elastase splits off the Fc portion of immunoglobulins in immune complexes and thus regulates inflammation by a feedback mechanism leading to cyclic inflammatory states.