Nasal polyps affect approximately 4% of the population in the western world. The etiology of this disease is unknown, although inflammatory mechanisms may play an important role. In preceding studies we and others have shown that besides H1-antagonism, azelastine influences the immigration and activation of inflammatory cells. In this open label study in 16 patients with nasal polyps and perennial mite-allergic rhinitis, the effect of azelastine nasal spray twice daily 0.14 mg to each nostril on recurrence of nasal polyposis after endonasal surgery was evaluated. One patient dropped out after 3 months, unwilling to take further medication. Clinical and laboratory data of 15 patients were recorded over 25 weeks in a total of seven visits. Of these one patient needed nasal budesonide during the 4 weeks between visits 3 and 4. All other patients did not take any steroids before inclusion into the trial or during the 6-month observation period. Concentrations of eosinophil cationic protein (ECP) for eosinophils, myeloperoxidase (MPO) for neutrophils and tryptase for mast cells were determined in nasal secretions before and after eight and 25 weeks of treatment using double antibody radioimmunoassays, because these have been demonstrated to be good inflammatory markers in nasal diseases. Mean concentrations of MPO decreased from 2724 ng/mL to 1610 ng/mL (p = 0.0015) over the entire treatment period. ECP decreased from 458 ng/mL to 264 ng/mL (p = 0.0342). Tryptase decreased from 37.9 ng/mL to 22.4 ng/mL (p = 0.0574). These data were consistent with a significant decrease in clinical symptoms. Thus, azelastine seems to have an inhibitory effect on eosinophil and neutrophil activation in patients with nasal polyps and mite allergy.