Rats were immunized with keyhole limpet hemocyanin (KLH) included in complete Freund's adjuvant (CFA) or with the same antigen absorbed to aluminum hydroxide gel. Incubation of their spleen and MLN cells with homologous antigen resulted in the formation of IgE-binding factors. The nature of IgE-binding factors formed by antigenic stimulation was different depending on the adjuvant employed for priming and the period after immunization. If the lymphoid tissues were obtained 2 to 4 wk after antigen priming, IgE-binding factors derived from lymphoid tissues of KLH-alum-primed animals selectively potentiated the IgE response, whereas those produced by the lymphoid tissues of KLH-CFA-primed animals suppressed the IgE response. Analysis of purified IgE-binding factors from KLH-primed spleen cells revealed that the factors were heterogeneous with respect to their m.w., and that IgE-binding factors of a m.w. of 13,000 were responsible for the biologic activities. Thus, the 13,000-dalton factors obtained from KLH-alum-primed spleen cells selectively potentiated the IgE response, and those from KLH-CFA-primed spleen cells suppressed the IgE response. The selective formation of either IgE-potentiating factors or IgE-suppressive factors by KLH-primed spleen cells was observed only when the cells were stimulated by specific antigen. When the same KLH-primed spleen cells were incubated with IgE, IgE-binding factors formed in the cultures neither potentiated nor suppressed the IgE response. It was also found that stimulation of a mixture of BCG-primed spleen cells and KLH-alum-primed spleen cells with PPD resulted in the formation of IgE-suppressive factors; the stimulation of the same mixed cell suspension with KLH resulted in the formation of IgE-potentiating factors. The results collectively indicate that the nature of IgE-binding factors is decided by antigen-primed cells.