The discovery by Isakson and Vitetta that a T lymphocyte-produced substance could induce lipopolysaccharide (LPS)-activated murine B lym phocytes to secrete IgG 1 (1) demonstrated that lymphokines could play a role in selecting the isotypes of antibody that are produced in an immune response. This observation became better defined when Vitetta, in col laboration with Ohara and Paul, traced this IgG I-inducing activity to a purified, recombinant lymphokine, now called interleukin-4 (IL-4)(2). Studies by Coffman and collaborators demonstrated that IL-4 could induce LPS-activated B cells to secrete IgE as well as IgG I, and that the lymphokine interferon-y (IFN-y) could inhibit this activity (3, 4). These observations were confirmed and extended by Snapper et aI, who dem onstrated that (a) larger doses of IL-4 were required to induce LPS activated B cells to secrete IgE than to secrete IgGI (5),(b) IFN-y, in addition to inhibiting IgG 1 and IgE production by B cells stimulated with LPS plus IL-4, could enhance LPS-induced IgG2a secretion, and (c) IL-4 could inhibit IgG2a secretion (6). Thus, differential secretion of IL-4 or IFN-y could regulate the relative quantities of IgGl, IgE, and IgG2a that were made following T cell-independent induction of a humoral immune response. IL-4 is also required for the stimulation of IgE, but not neces sarily IgG I, production in a T cell-dependent in vitro system in which B lymphocytes are cultured with antigen-specific T cells in the presence of the appropriate antigen (7, 8). Since single resting B cells can be induced in this system to generate, with high frequency, clones that include IgG 1 and IgE-secreting cells, it seems likely that membrane IgM+ B cells are being induced to switch to the production of IgG I and IgE. The results of this experiment do not differentiate, however, whether IL-4 promotes the actual Ig isotype switching process or selectively stimulates the growth of B cells that have switched to the secretion of IgG I or IgE by an IL-4-independent process. The hypothesis that IL-4 acts as an isotype switch factor, which may promote translocation of the Ig heavy-chain VDJ gene segment to a site close to the y 1 or aCH gene, is favored by observations that IL-4 can induce production of a germ-line yl mRNA transcript, and, in the presence of LPS, a germ-line a-chain mRNA transcript (9-12). The observation that exposure of resting, membrane IgG-B cells to IL-4 will allow these cells to make an IgG I response if they are subsequently stimulated with LPS in the absence of IL-4 is also more compatible with the hypothesis that IL-4 promotes a CIl to Cy I switch, rather than a selective proliferation of B cells that have undergone such a switch through an IL-4-independent process (13).