The effects of a three-month course of oral ketotifen on the histology and histochemistry of nasal mucosa, assessed on punch biopsy material, were studied in 30 adults with perennial allergic rhinitis. Ketotifen treatment was associated with reversal of the histopathology and enzyme changes in every case. Two months after stopping therapy, the rhinitis changes had returned in all 10 patients from whom posttreatment punch biopsies were taken. Other patients whose symptoms were relieved declined a third biopsy. Five normal volunteers were included as controls. The pretreatment mucosal biopsies showed variations in goblet cell population, thickened basement membranes, hypertrophied serous glands, diminished or absent mucus glands, and varying degrees of cellular infiltrates. There was marked edema with separation of collagen fibers and epithelial metaplasia especially in patients with long-standing allergy and nasal polyps. Ketotifen therapy was linked with reversal of the epithelial changes to normal, marked reduction in edema and cellular infiltration, and the retention of granules by mast cells. Changes in mucosal content of succinic dehydrogenase and acid phosphatase; high tissue levels of both which are associated with allergic rhinitis, also diminished towards the control levels during ketotifen therapy, only to return after its cessation.