Ly1+ B cells differ from conventional B cells with respect to their anatomical localization, cell surface marker expression, and antibody repertoire suggesting that they may constitute a functionally distinct subset of B cells. To determine whether Ly1+ B cells also have a developmentally distinct site of origin we grafted various fetal primordla Into adult severe combined Immunodeficient (scid) mice and analyzed their potential to give rise to T and B cells. We demonstrated that fetal omentum, but not spleen or thymus grafts, reconstituted exclusively Ly1 B cells(including the Ly1 sister population) as well as a population of IgM and IgA producing plasma cells In the spleen and gut, respectively. Although thymus grafts regularly reconstituted T cells, thymus plus fetal omentum cografts gave rise to apopulation of Ly1+ B cells as well as T cells which were also derived from omentum. However, In neither omentum nor omentum plus thymus cografts were conventional B cells detected. These results provide the first evidence thatLy1 B cells but not conventional B cells are generated from the fetal omentum. © 1991 Oxford University Press.