OBJECTIVE to utilize a double-blind protocol to provide clarification about the safety and effectiveness of levamisole in the treatment of recurrent aphthous stomatitis. METHODS Fourteen patients took a decreasing dose of oral levamisole for six months (initial dose 150mg three times a week) and ten others were placebo control patients. All were evaluated monthly. RESULTS The number of crises had a tendency to decrease in both groups, but without a difference between groups. The number of lesions diminished significantly in the two groups, but upon comparison the difference was not significant. Duration of the lesions diminished significantly in the placebo, however when compared to the levamisole group, difference was not significant during treatment. The intensity of pain was significantly lower in the two groups, but upon comparison, pain was significantly lower in the placebo group. The final global evaluation showed improvement in 50% of patients of the levamisole group and in 70% of the placebo, without a significant difference between treatments. No difference in the frequency of collateral effects was observed between groups. CONCLUSIONS Levamisole, as used in this protocol, is a safe drug. When compared with the placebo, levamisole is not effective in the prophylactic treatment of recurrent aphthous stomatitis. The placebo effect is important in diseases where emotional factors affect recurrence or expression of symptoms.