The murine Ly-I lymphocyte surface glycoprotein was defined initially with conventional antisera in cytotoxic assays (Cantor & Boyse 1977). As such, it appeared to be expressed exclusively on helper T cells (Cantor & Boyse 1975). Later, however. Fluorescence Activated Cell Sorter (FACS) analyses and sorting studies with monoclonal antibody reagents showed that all T cells express Ly-1, regardless of functional subclass (Ledbetter et al. 1980). Furthermore, these studies (Lanier et al. 1981a, 1981b) showed that Ly-1 is expressed on several murine B cell tumors and introduced evidence suggesting that this glycoprotein may also expressed on a small proportion of normal murine splenic B cells (Manohar et al. 1982, Hayakawa et al. 1983). Similar studies with human lymphocytes demonstrated the homologous {Leu-I) cell surface antigen on all normal T cells (Ledbetter et al. 1981), on some B cell tumors (particularly chronic lymphocytic leukemias)(Martin et al. 1981) and, as in the mouse, on a small proportion of apparently normal B cells (Calligaris-Cappio et al. 1982). Thus, a series of earlier findings foreshadowed contemporary evidence demonstrating Ly-I and Leu-1, respectively, on subsets of murine and human B cells and showing further that Ly-1 marks functionally distinct B cells that play a major role in autoimmunity in the mouse. In this paper, we summarize the physical and functional characteristics that distinguish Ly-1 B cells from the majority of splenic and lymph node (conventional) B cells. We focus on data from cell transfer and antibody treatment studies, which locate Ly-I B cells in a separate developmental lineage that branches off from the conventional lymphocyte developmental lineage during prenatal or early neonatal life. We then consider various genetic defects that influence autoantibody production and Ly-I B representation and, finally, we discuss potential homolog-