MRL/Mp mice are known to have autoimmune disease-prone genetic background, which contributes to the development of a lethal autoimmune disease at an early age in association with the lymphoproliferative gene, lpr. In this study, we found that MRL/Mp mice, not bearing lpr (MRL/Mp-(+)/+), spontaneously developed pancreatitis at a late stage of life, which was histopathologically characterized by destruction of pancreatic acinar cells with mononuclear cell infiltration. In female 34-38-weeks-old mice the incidence of pancreatitis reached 74%, whereas the male mice developed the disease with a reduced incidence, at a later stage of life and with a reduced severity. Cell infiltrates in the affected lesions were composed predominantly of CD4+ cells and to lesser extent Mac-2+ macrophages. Adoptive transfer of the spleen cells obtained from pancreatitis-bearing female mice generated pancreatitis in female normal mice, but not in the male mice. Transfer of the serum of pancreatitis-bearing mice failed to induce any pancreatic lesions. These findings indicate that pancreatitis in MRL/Mp-(+)/+ mice may be mediated by cellular autoimmune mechanism. This may present a useful concept for analysis of the developmental mechanisms of human chronic pancreatitis in an aspect of autoimmunity.