Anti‐2,4,6‐trinitrophenyl (TNP) IgE antibody response was elicited by stimulating TNP‐keyhole limpet hemocyanin‐primed murine spleen cells with the same antigen in vitro. The released anti‐TNP IgE was assayed by antigen‐ and isotype‐specific enzyme immunoassay developed in our laboratory. When prostaglandin E2 (PGE2) was added to the lymphocyte culture at 10−7 M, anti‐TNP IgE response was augmented two‐ to fourfold. Interestingly, PGE2 did not affect the production of anti‐TNP antibodies belonging to other isotypes including IgM, IgG1, IgG2a, IgG2b, IgG3 and IgA. Moreover, PGE2 showed neither enhancing nor interleukin 4‐replacing activities in the polyclonal IgE response by B cells stimulated with lipopolysaccharide and interleukin 4. When endogenous prostaglandin synthesis was inhibited by 10−6 M indomethacin, the anti‐TNP IgE response, but not the corresponding IgG response, was suppressed by 30%‐60%. These results suggest a potential role of PGE2 in the up‐regulation of the antigen‐specific IgE response.