Secretory leukoprotease inhibitor (SLPI) is a secreted glandular protein thought to regulate elastase activity and, more recently, to inhibit both mast cell chymase activity and histamine release from mast cells. To begin to examine the possible role of SLPI in humans, we determined the distribution of SLPI in the human nasal mucosa and quantitated the functional activity of SLPI in nasal lavage fluid. Immunochemical staining of the nasal mucosa revealed intense, selective immunoreactivity in the serous cells of the submucosal glands. The level of SLPI in nasal secretions was measured by enzyme immunoassay. In control subjects (n = 8), the level of SLPI in nasal lavage fluid (NLF) after saline challenge (baseline level) was 2.5 +/- 0.5 micrograms/ml, accounting for 3.3 +/- 0.6% of total protein in nasal secretions. After methacholine (MCh) and histamine (HIST) challenge, the level of SLPI increased to 7.0 +/- 1.4 and 6.1 +/- 1.6 micrograms/ml, respectively (both p < 0.05). In atopic patients (n = 8), the level of SLPI after MCh and HIST challenge increased from a baseline level of 7.6 +/- 2.0 micrograms/ml to 22.1 +/- 6.4 and 25.2 +/- 10.5 micrograms/ml, respectively. After allergen challenge, the concentration of SLPI increased significantly in atopic patients, whereas there was no increase in the level of SLPI in control subjects. Western blot analysis of MCh-induced nasal secretions revealed a single band with a molecular weight of 12 kD, the same as recombinant SLPI.(ABSTRACT TRUNCATED AT 250 WORDS)