Cultured cells from mouse thoracic duct, spleen, lymph node, Peyer's patches, and bone marrow gave rise to cells containing large amounts of cytoplasmic IgM, IgGl, and IgG2 when stimulated by bacterial lipopolysaccharide (LPS). Differntiation of IgA producers occurred in bone marrow only, and to a lesser extent than other classes. Significant IgM responses preceded development of cells containing other classes. The differentiation of IgG and IgA producers did not appear to depend on T cells, since cultures from nu/nu or thymectomized-irradiated, bone marrow-protected mice responded as well as normals. Cultures from mice rendered deficient in B cells by anti-mu treatment responded normally to T cell mitogens, but did not proliferate or give rise to immunoglobulin-secreting cells when stimulated with LPS. Bone marrow cultures gave relatively meager proliferative responses to LPS, but generated as many or more immunoglobulin-secreting cells as did other tissues.