The present study demonstrates that human rIL-4 is capable of inducing the secretion of IgE by PBMC. At a concentration of 200 U/ml, an IgE response was observed in 11/26 cultures of PBMC from normal donors and in 12/15 cultures from allergic individuals. The same rIL-4-stimulated cells released significant amounts of IgE-binding factors (IgE-BF) in their culture supernatant. These IgE-BF were shown for the first time to bind simultaneously to some mAb against Fc epsilon R II (mAbER) and to soluble IgE. The lack of correlation between the rIL-4-induced secretion of IgE-BF and IgE indicates that the production of IgE-BF or the expression of Fc epsilon R II is not the only factor involved in the induction of IgE synthesis by rIL-4. However, the observation that mAbER suppressed the rIL-4-induced IgE synthesis strongly suggests that either Fc epsilon R II or IgE-BF are necessary for an IgE response. Finally, the spontaneous in vitro synthesis of IgE by enriched B cell preparations isolated from atopic donors was suppressed in an isotype-specific manner by the same mAbER or by their F(ab')2 fragments. These observations suggest that the ongoing IgE synthesis by in vivo pre-activated B cells is also regulated by IgE-BF or Fc epsilon R II. It is concluded that Fc epsilon R II or IgE-BF play an essential role both in the induction of IgE synthesis by normal B cells and in the ongoing IgE synthesis by in vivo activated B cells from allergic donors.