Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of facial paralysis, facial oedema, and lingua plicata in association with other symptoms, such as headache and mental changes. Because the origin of this syndrome is still unknown, only symptomatic treatment is possible. In 18 patients suffering from MRS, whether with a complete or with an incomplete picture, we used the antileprosy drug clofazimine for therapy. A decrease in the frequency and intensity of oedema was achieved by this therapy in 94% of patients. However, improvement persisting throughout a follow-up period of up to 3 years was seen in only 62% of patients. We demonstrate that clofazimine is an alternative to glucocorticosteroids for the treatment of MRS.