Thalidomide has been advocated as the treatment of choice for recalcitrant aphthae. We describe the case of patient with HIV infection and extensive aphthae whose condition failed to respond to corticosteroids, cyclosporine, and thalidomide. The patient's course was complicated by colonic aphthae. Rapid and sustained resolution was achieved through treatment with granulocyte colony-stimulating factor, a previously unreported therapeutic option.