Intranasal corticosteroids have been shown to be more effective than oral antihistamines for the treatment of scasonai allergic rhinitis. However, there are some who question whether intranasalty administered corticosteroids should be used due to potential systemic effects. Fluticasone propionate, a potent corticosteroid with high specificity for the glucocorticoid receptor, is available as an aqueous nasal spray for the treatment of allergic rhinitis. To determine whether the efficacy of fluticasone propionate aqueous nasal spray (FPANS) was due to direct topical effects on the nasal mucosa or to indirect systemic effects following absorption from the nasal mucosa or from the swallowed portion of an intranasal dose. FPANS 200 μg once daily was compared with oral fluticasone propionate 5 mg or 10 mg once daily or placebo for 2 weeks in patients with seasonal allergic rhinitis. These oral dosages were chosen to yield low but consistent plasma fluticasone propionate concentrations. Both clinician- and patientrated scores for nasal obstruction, rhinorrhoea, sneezing, and nasal itching were significantly lower in the intranasal fluticasone propionate group compared with both oral fluticasone propionate groups. A separate plaeebo-controlled study was conducted in patients with perennial rhinitis to detennine if administration of FPANS 200 μg once daily Ibr 1 year was associated with adverse systemic effects. At the 1-year assessment, there were no significant eflects on bone mineral density or on biochemical markers of bone turnover. Similarly, there was no evidence of posterior subcapsular cataracts nor of glaucoma. Furthermore, there were no significant effects on hypothalamie-pituitary adrenal axis function as assessed by plasma cortisol and 24-h urinary cortisol response to the 6-h cosyntropin stimulation test. These data confirm that the eflicacy of FPANS for the treatment of allergic rhinitis results from direct topical eflects, thus reducing the likelihood of adverse systemic effects.