In the present investigation the occurrence of humoral immunity to pancreatic duct cells (PDC) was studied in 12 patients with Sjögren's syndrome (SS), 31 patients with rheumatoid arthritis (RA), and 64 controls. Four sera of patients with SS and eight of patients with RA produced diffuse cytoplasmic fluorescence of intro- as well as of interlobular PDC of human and rhesus monkey origin. All sera positive with PDC antigens gave also positive staining reaction with parotid, submandibular, and lacrimal duct cells. In absorption studies antibody activity to PDC and salivary duct cells could be absorbed equally well with human or monkey parotid gland or pancreas with almost identical antigen concentrations. These findings point to the presence of common antigenic determinants in the organs studied. Human thyroid microsomes and rat liver homogenate did not reduce antibody activity. The demonstration of antibodies to PDC in addition to the reported mononuclear cell infiltration of the pancreas point to the involvement of autoimmune mechanisms in pathogenesis of the commonly observed subclinical exocrine insufficiency in SS and in some cases of RA.