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The aim of the study was to assess the efficacy of 2 different concentrations of minocycline mouthwashes on the symptoms of recurrent aphthous stomatitis (RAS).The 2-year study was designed as a randomized, double-blind, crossover study. Healthy patients with frequent RAS episodes received 2 sealed and computer-randomized marked kits containing minocycline mouthwashes (0.2% and 0.5% solution). The patients were asked to use 1 of the kits on the first episode of RAS, starting with the first onset of prodromal symptoms, until the symptoms resolved or up to a maximum of 10 days (whichever came first). The patients were asked to use their second kit during a subsequent episode.A total of 14 patients (8 males, 6 females) completed the 2 arms of the study. The mean intensity of pain was significantly lower when the 0.5% solution was used compared with the 0.2% solution (P = .027). The difference reached the level of statistical significance as soon as the end of the second day of use (P = .032). Only minor and temporary adverse reactions were documented.We found that 0.5% minocycline mouth rinse was more effective than the 0.2% concentration, which had been suggested by our group in previous studies for the management of RAS.