Human neonate B lymphocytes display unique phenotypic and functional characteristics: in addition to CD1c antigens, CD5+ and CD5- subsets both express activation markers such as CD23 and Bac-1. They proliferate strongly in the presence of various lymphokines (rIL-2, rIL-4, low molecular weight BCGF), but differentiate poorly in the presence of the same lymphokines, pokeweed mitogen and Epstein-Barr virus. It has also been reported that human neonate B lymphocytes produce polyreactive autoantibodies after in vitro activation by Staphylococcus aureus Cowan I and transformation by Epstein-Barr virus. We now show that, in the absence of in vitro stimulation, human neonate B lymphocytes produce polyreactive antibodies of the IgM isotype against several autoantigens. The B lymphocytes involved expressed membrane IgD, IgM, CD23 and CD11b molecules; CD5 expression was variable. This phenotype was consistently found on a minority of B lymphocytes and is similar to that of polyreactive autoantibody-producing B cells in mice. We also found that autoantibody production in vitro could occur in the absence of any T helper effect. The function of these autoantibodies is not clearly established, but their occurrence in a large proportion of human neonates strongly suggests that they play an important role in the development of the immune system.