Schistosoma mansoni infection in the mouse has been shown to be accompanied by a down-regulation in parasite-Ag- and mitogen-induced Th1 cytokine secretion (IL-2 and IFN-gamma) with a simultaneous increase in the production of Th2 cytokines (IL-4, IL-5, and IL-10), suggesting a generalized imbalance in lymphocyte function. In the present study, we examined whether infection with S. mansoni would also influence the character of immune responses to a non-parasite Ag, sperm whale myoglobin (SwMb). When spleen cells (SC) from schistosome-infected SwMb-immunized animals were stimulated with SwMb, their production of IL-2 and IFN-gamma per CD4+ cell was found to be significantly reduced (by 45% and 59%, respectively) compared with the responses observed in immunized uninfected animals. Moreover, SwMb-induced secretion of IL-4 per CD4+ cell was increased threefold in SC cultures from infected mice. No myoglobin-induced IL-5 was detected in the same cultures. Addition to SC cultures of a neutralizing mAb specific for IL-10 partly restored the suppressed IFN-gamma response to SwMb seen in infected mice, suggesting a role for IL-10 in the observed down-regulation. S. mansoni-infected mice also showed an impaired antibody response to SwMb, with levels ranging from 10% to 27% of those observed in uninfected mice, although no differences in IgG isotype were evident. Taken together, these results suggest that infection with S. mansoni induces a down-regulation of Th1 responses and elevation of Th2 responses to unrelated foreign immunogens as well as to parasite Ag themselves. One implication of these findings is that helminth-infected individuals may have altered cell-mediated immune function to other microbial agents.