B-lymphocyte hybridomas, prepared by fusion of C57B1/6 spleen cells with the HGPRT lymphoma M12.4.1 in vitro, were stimulated with affinity - purified anti-IgM, the phorbol ester, PMA, bacterial lipopolysaccharide, LPS, or with cytochalasin B (CB). Six different hybridoma lines differentiated to give 10-15% IgM-secreting cells after 3 days in culture with anti-IgM. Five of the six differentiated after exposure to LPS, two after exposure to PMA, and one after exposure to CB. The effect of anti-IgM, but not of the other stimulants was inhibited by the IgM myeloma protein, MOPC 104E; the effect of the PMA, but not the other stimulants was inhibited by retinoic acid. Cell lines which were differentiating, regardless of inducing agent, showed a 50% reduction in expression on cell membrane Ia antigens, and a slowing of cell division of about 50%.