SummaryAfter oral administration of cysts of the intestinal protozoan parasite, Giardia muris, young male C3H/He mice are chronically infected, whereas BALB/c mice demonstrate a rapidly resolving pattern of infection. Both strains of mice injected with trophozoites in adjuvant and challenged orally with cysts develop serum antibodies to numerous trophozoite proteins. A limited number of these protein antigens was differenliatly immunoprecipitated by sera from resistant BALB/c and susceptible C3H/He mice exposed to G. muris. 35S‐methionine‐labelled protein antigens better recognized by immune BALB/c sera included molecules of relative mobility (Mr) 82,000 and a series of proteins of Mr 25,000 to 32,000, Differential recognition extended to a subset of solubilized trophozoite antigens that bind to the Iectin. wheat germ agglutinin (WGA), and that can be radio‐iodinated. In particular, a complex of 4 acidic protein antigens of approximate Mr 32,000. and designated collectively as Gm32, was better recognized by immune BALB/c serum than C3H/He serum. Isolated WGA‐binding antigens were not able to consistently vaccinate BALB/c mice against subsequent G. muris infection. Moreover, preliminary evidence has been obtained that lack of antibody responsiveness to Gm32 does not segregate strictly with susceptibility to chronic infection in (BALB/c × C3H/He)F2 mice. These data, plus the observation that drug‐cured C3H/He mice are highly resistant to reinfection, has led to examination of whether mice differ in the capacity of the intestines to support inflammatory responses. Mast cell deficient Wf/Wf mice, unlike wild‐type litter‐mates, developed chronic giardiasis although no reconstitution of resistance has yet been achieved with inocula of bone marrow cells from +/+ mice. BALB/c mice injected with the antihistamine and antiserotonin drug, cyproheptadine, also showed prolonged infections with G. muris. The data suggest that analysis of specificity differences in immune responses of mice varying in susceptibility to intestinal parasites must be supplemented by examination of the capacity of the intestine to support induced immune responses.