Trichloroethylene (TCE) is suspected as a potent immunomodulator that accelerates the development of allergic diseases. We previously reported that TCE promotes ovalbumin (OVA)-induced active cutaneous anaphylaxis, including enhancing antigen-specific serum IgE levels and splenic lymphocyte proliferation. However, the target cells and molecular mechanism through which TCE modulates antigen-specific immune responses remain unclear. To identify a potential underlying mechanism, we investigated whether TCE modulates T cell receptor (TCR)-induced T cell activation and proliferation in vitro. TCE enhanced T cell proliferation primed by anti-CD3 antibody, but not concanavalin A, in a dose-dependent fashion. In addition, TCE enhanced anti-CD3-primed proliferation of CD8⁺ rather than CD4⁺ T cells. Consistent with this result, TCE markedly enhanced the Lck phosphorylation mediated by anti-CD3 antibody in CD8⁺ but not CD4⁺ T cells. Furthermore, we analyzed the effect of TCE exposure via drinking water for 2 weeks on splenocyte populations in non-immunized and OVA-immunized mice. In OVA-immunized mice, TCE (3 mg/l) significantly expanded CD3⁺, CD8⁺ and CD4⁺ cell populations, however the effect at the lower concentration was significant only in the CD8⁺ populations, whereas TCE had no effect on these cells population in non-immunized mice. These findings suggest that TCE enhances TCR-CD3-induced proliferation of CD8⁺ rather than CD4⁺ cells and disrupts various activities of peripheral T cells.