A human B cell subpopulation identifiable by the expression of the cell surface antigen Leu-1 (CD5) is responsible for most of the immunoglobulin M rheumatoid factor secreted in vitro after the cells are stimulated with Staphylococcus aureus. The ability of B cells bearing the Leu-1 marker (Leu-1⁺) to secrete rheumatoid factor is present early in development and extends to adulthood, since Leu-1⁺ B cells from cord blood and from peripheral blood lymphocytes of both normal adults and patients with certain autoimmune conditions secrete rheumatoid factor in comparable amounts. The neonatal enrichment of Leu-1⁺ B cells, the presence of Leu-1⁺ B cells in increased frequencies in patients with autoimmune disease, and the involvement of Leu-1⁺ B cells in autoantibody secretion suggest both developmental and functional homologies between this human B cell subpopulation and the murine Ly-1 B cell subpopulation.