Malaria and helminth infections are two of the most prevalent parasitic diseases globally. While concomitant infection is common, mechanisms contributing to altered disease outcomes during co-infection remain poorly defined. We have previously reported exacerbation of normally non-lethal Plasmodium yoelii malaria in BALB/c mice chronically infected with the intestinal trematode Echinostoma caproni. The goal of the present studies was to determine the effect of helminth infection on IFN-gamma and other key cytokines during malaria co-infection in the P. yoelii-E. caproni and P. yoelii-Heligmosomoides polygyrus model systems. Polyclonally stimulated spleen cells from both E. caproni- and H. polygyrus-infected mice produced significantly lower amounts of IFN-gamma during P. yoelii co-infection than malaria-only infected mice. Furthermore, the magnitude of IFN-gamma suppression was correlated with the relative amounts of IL-4 induced by these helminths (E. caproni=low; H. polygyrus=high), but not IL-10. Concurrent malaria infection also suppressed helminth-associated IL-4 responses, indicating that immunologic counter-regulation occurs during co-infection with malaria and intestinal helminths.