Although certain helminth infections preferentially induce type 2 T-cell responses, the immunological mechanisms responsible for type 2 T-cell polarization remain unclear. In the present study, we investigated the effects of excretory-secretory (ES) antigen from the nematode Nippostrongylus brasiliensis on cytokine production by mesenteric lymph node (MLN) cells isolated from naive rats. MLN cells produced considerable levels of gamma interferon (IFN-) during a 72-h stimulation with concanavalin A (ConA) or with immobilized anti-CD3 plus soluble anti-CD28 antibodies (anti-CD3/CD28). With either stimulation, 10 µg of ES antigen per ml significantly suppressed IFN- and interleukin-2 (IL-2) production without cytotoxic activity. The copresence of anti-IL-4, anti-IL-10, or transforming growth factor  (TGF-) blocking antibodies did not alter the suppressive effect of ES antigen on IFN- production. ES antigen did not affect IL-10 production. Kinetic studies of the effect of ES antigen indicated that the antigen suppressed even ongoing IFN- production. Reverse transcription-PCR study showed that in the presence of ES antigen, IFN- mRNA expression by MLN cells was suppressed 6 and 12 h after ConA or anti-CD3/CD28 stimulation. ES antigen also significantly suppressed IFN- production by purified CD4⁺ or CD8⁺ T cells during anti-CD3/CD28 stimulation but did not affect IL-4 production by CD4⁺ T cells. These findings suggested that the nematode antigen suppressed production of IFN- and IL-2 but not IL-4 or IL-10 production. ES antigen-mediated suppression of IFN- during the initiation of the immune response may provide a microenvironment that helps generation of type 2 T cells.