Seasonal allergic rhinitis is characterized by the development of nasal mucosal inflammation in response to natural allergen exposure, and is prevented by the administration of topical corticosteroids. Interleukin-4 (IL-4), IL-5, and IL-6 may have important roles in this process, and in vitro the gene transcription for each of these cytokines is inhibited by corticosteroids. In this study we have therefore investigated the effect of seasonal allergen exposure on the expression of immunoreactivity for IL-4, IL-5, and IL-6 in nasal mucosal biopsies, and the effect of regular prophylactic treatment with the topical corticosteroid, fluticasone propionate. Following a nasal mucosal biopsy out of season, patients were randomized double-blind to receive 6 wk of treatment during the pollen season with either topical fluticasone nasal spray (200 micrograms daily) or matching placebo. Each subject underwent a repeat nasal biopsy at the end of the 6-wk treatment period. Seasonal increases in epithelial eosinophils (p = 0.046), submucosal eosinophils (p = 0.001), and epithelial mast cells (p = 0.055) occurred in the placebo--but not the fluticasone-treated patients. Submucosal mast cell numbers did not change in either group. Immunoreactivity for IL-4 and IL-6 was localized predominantly to mast cells while IL-5 was found in both mast cells and eosinophils. Numbers of IL-4+ cells in the nasal submucosa were significantly suppressed by treatment with fluticasone (p = 0.0003 for monoclonal antibody [mAb] 3H4, p = 0.041 for mAb 4D9). In contrast, fluticasone treatment failed to influence the number of IL-5 and IL-6 immunoreactive cells.(ABSTRACT TRUNCATED AT 250 WORDS)