Azelastine (azelastine hydrochloride) was orally administered to 43 patients with recurrent aphthous ulcers (RAU), and its clinical effects and in vitro influence on leukocytes were examined. During at least 6 months after drug treatment, no oral ulcers occurred in 7 patients, and an improvement of the oral condition was exhibited in all except 4 of the remaining patients. The frequency of occurrence of RAU was significantly reduced, from 1.7 +/- 0.9 to 0.9 +/- 0.5 times/month, and ulcer duration and oral irritation were also significantly reduced from 12.5 +/- 2.5 and 7.5 +/- 2.4 days to 9.8 +/- 2.6 and 5.3 +/- 2.4 days, respectively. Neutrophils from patients treated with Azelastine generated a suppressed volume of superoxide (O2-). Suppression of O2- generation and chemiluminescence by in vitro Azelastine was also confirmed to occur in a dose-dependent manner. Furthermore, the production of TNF-alpha and GM-CSF in lymphocytes was suppressed in the presence of Azelastine, and the drug protected sheep red blood cells and epithelial tumor cell lines against hydrogen peroxide impairment and hypotonic shock. These clinical and experimental results lead to the conclusion that improvement of RAU by Azelastine depends on the protection of cell membranes and the suppression of leukocyte-function, including reactive oxygen generation.