Exposure to an acute laboratory stressor at the time of keyhole limpet hemocyanin (KLH) immunization results in a long-term suppression in circulating anti-KLH antibody. The mechanism for the stress-induced reduction in anti-KLH immunoglobulin (Ig) remains unknown. Given that the generation of anti-KLH antibody requires T cell help, we hypothesize that stress reduces the proliferation of anti-KLH T cells, thus leading to a reduction in anti-KLH antibody. The present studies examined the effect of tail shock stress (100, 1.6 mA, 5-s, 60 s ITI) on the KLH specific T cell response. Fischer F344 rats were immunized either intraperitoneally (i.p.) or subcutaneously (s.c.) at the base of the tail with 200 microg KLH, and exposed to inescapable tail shock (IS) or remained in their home cages (HCC). T cell proliferation after KLH restimulation, but not ConA, was markedly suppressed in IS animals in both the spleen after i.p. immunization and the draining lymph nodes after s.c. immunization. Other secondary lymphoid cells did not differ in their proliferative capacity. Anti-KLH IgG, IgG1 and IgG2a, but not anti-KLH IgM serum levels were significantly suppressed. These data support the conclusion that stress suppresses the generation of antigen specific T cells. In addition, the methods employed in the current study allow the isolation of the site of the acquired T cell immune response, making it possible to further elucidate the cellular mechanisms that contribute to stress-induced modulation of the antigen-specific acquired immune response.