This study documents the autoregulation of B cell growth by an IgM autoantibody. This autoantibody is secreted by B lymphocytes upon stimulation by polyclonal activators and is identified by its potent inhibition of B cell growth induced by these agents (endotoxin, Fc fragment of human gamma-globulin, Mycoplasma bovirhinis, and anti-mouse Ig). The autoantibody specifically affects B cells: there was no effect on mitogen- or antigen-induced T cell proliferation and of responses to interleukin 1, interleukin 2, or interferon. Nonspecific effects were excluded by the ineffectiveness of serum and myeloma IgM. Also, IgG-IgM immune complexes were excluded. The binding specificity of the IgM autoantibody is not yet defined but appears to be a B cell surface structure distinct from membrane Ig. The autoantibody constitutes a ubiquitous, autoregulatory influence on B cell growth, which may be an important component in physiologic and pathologic states of B cell homeostasis.