Use of zinc sulfate in promotion of wound healing and in maintenance of epithelial integrity suggested its possible use in the treatment or prevention of recurrent oral ulcers. In a series of 32 patients with recurrent aphthous ulcers (RAU), serum zinc levels were observed. Seventeen patients, eight with initial serum zinc levels above 110microng/dl and nine with serum zinc levels below 110microng/dl, were provided zinc sulfate supplementation up to a total of 660 mg/day. All patients with initial serum zinc levels less than or equal to 110 microng/dl showed improvement; three of the eight patients with initial serum zinc levels above 110 microng/dl improved, five did not. Improvement consisted of 50% to 100% reduction in frequency of episodes. This suggests a combination of causes of RAU, one of which may be a local or general deficiency of zinc or a defect in metabolism, perhaps at the cellular level, related to zinc.