Recurrent aphthous stomatitis (RAS) is characterized by necrotizing ulcers of the oral mucosa that persist, remit, and recur for variable periods of time. Despite the benign nature of the disease, persistent pain and ulceration may disable patients from performing their daily activities. We describe three patients with long-standing active RAS treated with oral colchicine. All patients experienced a marked decrease in symptoms and a remission of the disease. Recurrences, however, occurred within three days of discontinuation of the therapy. In one patient, colchicine therapy was discontinued because of persistent diarrhea. In another, a second remission was more difficult to achieve on the same regimen. The literature on the subject is reviewed, and the beneficial effects of colchicine therapy are discussed in relation to the immunopathogenesis of this disease. We conclude that colchicine therapy should be considered as an alternative in the treatment of the major or persistent form of RAS.