Trypanosoma cruzi, an intracellular protozoan parasite infecting a wide variety of vertebrates, is the agent responsible for Chagas disease in humans. An estimated 15-20 million people in South and Central America are infected with the parasite. Chagas disease often results in severe autoimmune and inflammatory pathology and is the major cause of heart failure in endemic areas. Nevertheless, little is known about the host-parasite interactions that lead to this pathology. We have previously cloned several members of a large gene family (SA85-1) and shown that these genes encode 85-kDa T. cruzi, mammalian-stage-specific, surface antigens. Here we report that members of the SA85-1 family possess sialidase activity and are shed by the parasite. We suggest that the sialidases may contribute to the pathology during T. cruzi infection by cleaving sialic acid from cells of the immune system.