Mixed-parasite infections are common in many parts of the world, but little is known of the effects of concomitant parasite infections on the immune response or on disease progression. We have investigated the in vivo effects of a chronic gastrointestinal nematode infection on the infectivity and development of the immune response against the common trematode helminth Schistosoma mansoni. The data show that mice carrying an established chronic Trichuris muris infection and coinfected with S. mansoni, had significantly higher S. mansoni worm burdens than mice without coinfection. The increase in S. mansoni worm burden was accompanied by a higher egg burden in the liver. Kinetic analysis of S. mansoni establishment indicate reduced trapping of S. mansoni larvae during skin-to-lung migration, with T. muris-induced alterations in lung cytokine expression and inflammatory foci surrounding lung-stage schistosomula, suggesting that the immunomodulatory effects of chronic T. muris infection elicited at the gut mucosal surface extend to other organs and perhaps specifically to other mucosal surfaces. The data show that a preexisting chronic gastrointestinal nematode infection facilitates the survival and migration of S. mansoni schistosomula to the portal system, and as a result, increases the egg burden and associated pathology of S. mansoni infection.Helminth infections are among the most common infections of humans (2,7,26). Helminth infections are characteristically chronic in nature, and in order to achieve such long-lasting infections, these parasites have developed sophisticated survival strategies such as secretion of immunomodulatory substances and/or the induction of regulatory immune responses (35). These immunomodulatory activities may alter immune responsiveness to third party antigens such as vaccines (9, 10, 18, 42) and concurrent infections (reviewed in references 4 and 27). Intriguingly, recent studies have also demonstrated that the immunomodulatory effects of helminth infections may have beneficial effects, such as controlling allergy and inflammatory diseases (19,53).Individuals living in areas where helminths are endemic often carry more than one species of worm infection; egg output for an individual helminth species is often higher in individuals carrying mixed infections than in individuals carrying singlespecies infections (3,5,20,38,45), which may reflect higher intensities of infection and so a higher risk of morbidity. Geographical and environmental factors are known to be of significance in facilitating this type of polyparasitism: for example, similarities in the transmission pathways for certain soil-transmitted nematodes are likely to account for some of the observed associations. However, significant associations have also been demonstrated between helminth infections that do not share obvious transmission pathways and some of these associations are not explained solely by household or environmental effects (20). Furthermore, the intensity of helminth infections alters the risk of multipl...