Host survival during schistosomiasis requires the development of a tightly regulated and Th2-polarized immune response against parasite egg Ags. In this system, Th1 response suppression has been thought to be enforced through the production of IL-10 by Th2 cells and natural T regulatory (Treg) cells. By comparing Th responses in schistosome egg-injected mice that lack IL-10, IL-4, and/or Treg cells, we have been able to build a detailed picture of the relative contributions of Treg cells, Th2 cells, and IL-10 to regulation of the egg-induced response. Our data indicate that eggs induce a marked Treg cell response, evident as the extensive proliferation of Foxp3(+) cells that is proportionally as great as the response occurring within the Th compartment. Furthermore, we show that Treg cells prevent Th1 response development and limit the magnitude of the Th2 response. Although Treg cells are able to produce IL-10 after egg injection, we found no evidence for a role for IL-10 in Treg-mediated suppression of Th cell responses, nor did we find evidence for an inhibitory effect of Th2 cells on Th1 response development. Thus, the magnitude and phenotype of the egg-induced effector Th response are controlled by a parallel response within the Treg population.