After vaccination with tetanus toxoid (TT), TT-specific immune responses in humans infected with Schistosoma mansoni were assessed. Peripheral blood mononuclear cells (PBMC) from vaccinated infected subjects and vaccinated uninfected controls were evaluated for their ability to produce cytokines characteristic of Th1 or Th2 cells (interferon [IFN]-gamma or interleukin [IL]-4, respectively) after in vitro restimulation with TT. TT-specific IFN-gamma production by PBMC from infected subjects was inversely related to infection intensity and was significantly lower than TT-specific IFN-gamma production by control PBMC. PBMC from all of the infected subjects and 3 of the 5 controls analyzed by reverse transcriptase-polymerase chain reaction transcribed the IL-4 gene in response to TT restimulation. Together, these results suggest that S. mansoni-infected persons mount a Th2-like response to the bystander antigen TT, while uninfected persons mount a Th1- or Th0-like response.