Allergic rhinitis is associated with specific histopathologic changes in the nasal mucosa including squamous metaplasia and local eosinophilia. Previous studies have shown that mometasone furoate aqueous nasal spray is effective and well tolerated in reducing perennial rhinitis and seasonal allergic rhinitis symptoms. We undertook a multicenter, open-label study to evaluate, by nasal biopsy, the tissue changes associated with mometasone furoate use (200 microg/day) during a 12-month treatment period in patients with perennial rhinitis. Of the 69 patients enrolled in the study, 52 completed all 12 months of treatment. Nasal biopsy specimens obtained from patients at baseline and after treatment were evaluated in a blinded fashion by computerized image analysis, qualitative histologic examination, and immunocytochemistry. Morphologic examination of nasal biopsy specimens showed a decrease in focal metaplasia, no change in epithelial thickness, and no sign of atrophy after treatment with mometasone furoate. Immunocytochemical analyses of nasal biopsy specimens obtained before and after treatment revealed a significant decrease in major basic protein-positive eosinophils and tryptase-positive mast cells in the epithelium and lamina propria after treatment. Mometasone furoate appeared to attenuate the inflammatory process by reducing the extent of inflammatory cell infiltration, particularly of eosinophils. This study demonstrated that long-term administration of mometasone furoate is not associated with adverse tissue changes in the nasal mucosa of patients with perennial rhinitis.