Free submandibular salivary gland transfer was investigated as a surgical method for the treatment of severe keratoconjunctivitis sicca. In an animal model, we examined the tolerance of warm ischemia of the submandibular gland. After temporary interruption of the blood supply (1 to 6 hours), the morphologic changes in the submandibular gland were analyzed histologically and immunohistochemically in 41 rabbits. From 1.5 hours ischemia onward, an increasing structural damage of the parenchyma with emphasis on the secretory cells was seen. Six hours of ischemia caused total necrosis of the salivary gland. Our clinical experience includes 24 highly selected patients suffering from keratoconjunctivitis sicca, in whom we transferred 31 autologous submandibular glands to the temple for permanent autologous tear substitution within the past 4 years. The glands were implanted into a pocket prepared in the temporalis muscle, and the nourishing vessels were anastomosed to the superficial temporal artery and vein. The submandibular duct was implanted into the upper lateral conjunctival fornix. The transferred glands were left denervated. In addition to the clinical examination, scintigraphy with Tc 99m pertechnetate was used to document the graft's viability after the transfer. Viable incorporation with longstanding secretory function occurred in 26 of the 30 transplanted denervated salivary glands. The resulting lubrication of the treated eyes was irregular for up to 3 months in almost every case. One year after surgery, all patients with a viable transplant developed at least occasional epiphora, which was surgically managed by reducing the size of the graft in 10 patients. No severe side effects were seen in this series. The ophthalmologic evaluation of the method included the assessment of dry eye symptoms and of the volume and quality of ocular lubrication (Schirmer test, fluorescein break-up time), the pathology of the ocular surface (rose bengal staining), and the need for pharmaceutical tear substitutes. One year after surgery, 18 of 27 cases assessed were judged as significantly improved by these tests.