In the present study, we showed that both male and female nonobese diabetic (NOD) mice simultaneously develop frequent lymphocyte infiltrations in salivary submandibular glands (sialadenitis), very similar to those reported in the salivary glands of patients with Sjögren syndrome. These lesions were observed only in mice with pancreas exhibiting insulitis. The incidence of sialadenitis increased with the severity of insulitis. At the initial stage, small focal infiltrates were predominantly located around blood vessels. In older animals, inflammatory cells surrounded blood vessels and ducts. Most of the infiltrating cells proved to be L3T4+, whereas Lyt-2+ cells were comparatively few. Autoantibodies against duct epithelial cells were shown, but the degree of tissue invasion was not related to the existence of such antibodies. Antinuclear antibodies were also observed. These salivary gland infiltrates could be transferred in vivo to NOD neonates of both sexes by splenic T lymphocytes as well as by total spleen cells. These results suggest that sialadenitis in NOD mice is T cell mediated and may be related to insulitis.