The upper airway epithelium is coated with fibronectin, a glycoprotein that covers receptor sites for gram-negative bacteria and prevents them from colonizing the oropharynx. We investigated the identity of salivary proteolytic enzymes capable of degrading fibronectin in a group of 16 patients who had elective cardiac surgery. Six patients became colonized with gram-negative bacteria (Group C) and 10 did not (Group NC). Salivary elastase activity was low in both groups preoperatively. Twenty-four hours after surgery, salivary elastase activity increased in Group C, and it remained elevated at 48 and at 72 h. Fibronectin digestive activity of the saliva of patients in Group C was also increased within 24 h of surgery, and salivary elastase and fibronectin digestive activity were highly correlated (r = 0.86, p less than 0.001). Enzyme inhibition experiments showed that most of the fibronectin digestive activity was due to elastase from polymorphonuclear cells (PMN), and the molecular weight of the salivary enzyme digesting fibronectin was 30,000 daltons (similar to the molecular weight of elastase). Levels of antileukoprotease, the major elastase inhibitor in saliva, were normal in patients with increased elastase activity. We conclude that salivary elastase is of PMN origin, increases prior to gram-negative bacillary colonization of the pharynx, and is responsible for most of the fibronectin digestive activity of the saliva.