Since zinc deficiency has been shown to have a profound effect on the immune system of the mouse, it was of interest to evaluate the effects of the deficiency on host resistance to infection. The parasite Trypanosoma cruzi, which infects millions of South Americans each year, was chosen for study. Balb/c mice were fed to either zinc-deficient (1.0 micrograms Zn per gram), restricted (51 micrograms Zn per gram) or zinc-adequate diet (51 micrograms Zn/g). After 8 days on the purified diets, part of the mice from each dietary group were infected with 5 x 10(4) T. cruzi, a dose of this subline of the parasite that was normally sublethal. Twenty-two days postinfection, 80% of the mice in the infected zinc-deficient group were dead. The only other death (10%) occurred in the restricted, infected group. Prior to death the infected zinc-deficient group had a parasitemia that was 50 times greater than that of infected mice from the restricted or zinc-adequate groups. In all infected dietary groups, food intake and/or body weights were reduced in comparison to their uninfected counterparts. The data suggest that zinc deficiency and T. cruzi interact synergistically to profoundly alter both the nutritional and immune status of the host. The experiments also demonstrate the extreme vulnerability of zinc-deficient mice to some pathogens.