Twenty-two patients with aqueous tear deficiency (ATD) were examined for the presence of the following autoantibodies: immunofluorescent antinuclear antibody (ANA) and Sjögren's syndrome antibodies A and B (SS-A and SS-B). These autoantibodies were found in 17 (82%) patients but not in control subjects, and they correlated with the severity of symptoms and ocular surface changes. Bacterial keratitis, often recurrent and bilateral, and progressive sterile corneal stromal melting developed in six autoantibody-positive ATD patients. Eight antibody-positive patients had labial salivary or lacrimal gland biopsies, and all showed similar histologic features with marked destruction of the glandular architecture by lymphocytic infiltration. Immunoglobulin and complement were not detected in the glandular tissue. Circumstantial evidence suggests that an abnormal immunologic reaction, possibly related to Epstein-Barr viral (EBV) infection, is the cause of the glandular destruction and tear deficiency.