IL-4 is obligatory for primary IgE responses, whereas primary IgG1 and secondary IgE responses are partially IL-4 independent. To investigate the effect of IL-4 on the antigen-specific memory formation for these isotypes, BALB/c mice were treated after primary TNP-KLH immunization with recombinant IL-4 for a period fo 4 months. This prolonged presence of a high IL-4 level resulted in increased serum levels of total IgG1 and IgE, whereas total IgG2a did not change. The expression of CD23, but not I-Ad, increased on the splenic B cells. IL-4 treatment did not affect the IL-4 production by Con A stimulated spleen cells, whereas it did decrease the IFN-gamma production. In the same mice the TNP-specific IgG1 and IgE serum levels, however, were decreased. Similar results were found when the antigen was continuously present during the IL-4 treatment. Furthermore, it was shown that IL-4 decreased the formation of IgG1 and IgE memory cells. These results point to different effects of IL-4 in regulating antigen-specific and bystander responses.