Priming of CBA/J mice with different doses of antigen has a profound effect on the ratio of IgE versus IgG antibodies appearing upon Immunization. Repeated injections of minute doses induce IgG and high titers of IgE antibodies. Large doses elicit a high IgG but a very low IgE antibody titer. In order to study the modalities for activation and inactivation of IgE-producing B cells, an in vitro culture system was established in which spleen cells from animals primed with keyhole limpet hemocyanin were re-stliulated with antigen. In contrast to the expectation from the in vivo situation, spleen cells from animals Immunized with large doses of antigen and virtually lacking IgE antibodies produce high amounts of IgE antibodies upon re-stimulation in vitro. The titers in spleen cell cultures from mice primed with minute doses remain proportional to the response measured as serum antibodies. In accordance with the induction of high amounts of IgE antibodies in spleen cell cultures from mice primed with large doses, the frequency of IgE antibody-secreting cells was raised drastically, ∼1000-fold. The in vitro response is a true anamnestic response. The sudden appearance in high frequency of IgE antibody-forming cells among spleen cells isolated from primed mice which have high IgG but virtually no IgE antibody titers is as yet unexplained and the origin of the Bε memory cells has not yet been traced. The answer might be crucial for our understanding of the down-regulation of the IgE Immune responses.