When B cells from BALB/c mice were cultured with lipopolysaccharide (LPS) and interleukin-4 (IL-4), a large amount of IgE was detected in the culture supernatants. The IgE production from unseparated spleen cells cultured with LPS and IL-4 was less than the amount of IgE obtained from separated B cells. When syngeneic T cells were added to separated B cells cultures, which were subsequently stimulated with LPS and IL-4, less IgE was produced, as compared to cultures without T cells. The hypothesis that T cells, or factors secreted by these cells, inhibit IgE production is supported by the fact that the degree of suppression of IgE production paralleled the number of T cells added. CD8(+)-enriched T cells were slightly more suppressive than CD4(+)-enriched T cells. Addition of exogenous IL-3 was only partially suppressive. These observations suggest that IL-4 added to unseparated spleen cells in vitro stimulates B cells for IgE production and also stimulates T cells. Lymphokines secreted by these stimulated T cells may in turn act on B cells. Some of these lymphokines, such as interferon-gamma and IL-2, may have a suppressive action on IgE production.