Long term B lineage chimeras are used here to study the origin of plasma cells in the mouse. Chimeric mice are constructed by reconstituting lethally irradiated mice with peritoneal cells (PerC) and bone marrow cells from congenic pairs of mice differing in Igh-C allotype. All conventional B cells in these mice express the allotype of the bone marrow donor and nearly all Ly-1 B lineage cells express the allotype of the PerC donor. FACS analysis and immunohistology of these mice shows that virtually all (sig+) B cells in peripheral lymphoid organs are derived from the bone marrow donor. However, despite this overwhelming number of bone marrow-derived B cells in these animals, immunohistological staining of lymphoid organs and gut shows that nearly half of the IgM, IgG, and IgA plasma cells derive from the PerC donor. These data demonstrate that the peritoneal cavity contains a major reservoir of self-replenishing cells that play a significant role in the mucosal immune response. The possibility that these are B cells that belong to the Ly-1 B lineage is discussed.