We have studied the ability of various bacteria to stimulate human lymphocytes to produce leukocyte migration inhibitory factor (LIF). Mononuclear cells from adult and cord blood as well as purified T and B lymphocytes were stimulated with killed bacteria. The culture supernatants were tested for the presence of LIF by the agarose migration method. All nine bacterial strains tested activated unseparated mononuclear cells and B lymphocytes but not T cells to produce LIF. LIF was also present in cord blood cell cultures suggesting that the stimulation of lymphocytes was polyclonal rather than antigenic. Therefore, we propose that one of the physiologic functions of B lymphocyte lymphokines might be to form part of the nonspecific defense mechanisms against microbial invasion.