The ability of antigen‐specific IgE antibodies to modulate the in vivo antibody response was studied by comparing the antibody response in mice immunized with 2,4,6‐trinitrophenyl (TNP)‐specific monoclonal IgE followed by bovine serum albumin (BSA)‐TNP or with BSA‐TNP alone. The serum IgG antibody response against BSA, measured in enzyme‐linked immunosorbent assay ELISA, was enhanced up to 100‐fold in groups receiving IgE. The enhancement required specific interaction between IgE and antigen, since no effect was seen when unconjugated BSA was used as antigen. Polyclonal activation by IgE/antigen complexes did not occur. IgE given 24 h after specific antigen had no stimulatory capacity. Pretreatment of the mice with Fee receptor type II (FcϵRII)‐specific monoclonal antibody completely inhibited the IgE‐mediated enhancement. Thus, the data demonstrate for the first time an in vivo role for FcϵRII in enhancement of specific antibody production.