Stimulation of rabbit mesenteric lymphocytes with antiimmunoglobulin antibody (anti-Ig) for 24 hr (first stage of culture) followed by the addition of enhancing soluble factor (second stage of culture) induced the formation of IgG. The presence of mitotic inhibitors, such as cytosine arabinoside (Ara-C), hydroxyurea (HU), with anti-Ig for the first 24 hr of incubation did not inhibit the production of IgG induced by anti-Ig and soluble factor. The addition of cytochalasin-B in the first stage of culture with anti-Ig did not inhibit, but rather enhanced, the formation of IgG. On the other hand, the presence of Ara-C, HU, or cytochalasin-B with soluble factor in the second stage of culture completely inhibited the production of IgG. Soluble factor preferentially induced the uptake of thymidine of anti-Ig-stimulated cells. Lipopolysaccharide (LPS) also induced the proliferation of rabbit lymphocytes, but did not induce the IgG production of anti-Ig-stimulated cells. However, LPS-stimulated cells formed a significant amount of IgG when they were cultured with soluble factor. Anti-Ig-stimulated cells absorbed the enhancing activity of soluble factor, but non-stimulated cells did not absorb the activity. These results showed that cross-linkage of Ig receptors or LPS receptors with anti-Ig or LPS induced the formation of acceptor sites for soluble factor without the requirement of cell division and these activated cells started to proliferate and maturate to antibody-forming cells under the influence of soluble factor.