Macrophages in Peyer's patches are important in the initiation of gastrointestinal immune responses to enteric pathogens. To examine their potential role in giardiasis, murine mononuclear cells were isolated from collagenase-treated Peyer's patches by their adherence to glass. These cells were incubated with Giardia lamblia trophozoites in the presence of nonimmune or immune (anti-Giardia antibody titer, greater than or equal to 1:1,024) mouse serum. Macrophages ingested trophozoites at low levels when they were incubated with nonimmune mouse serum. Ingestion was significantly increased at all time points (P less than 0.01) when cells and parasites were incubated in 5% immune mouse serum; the number of Giardia trophozoites ingested per 100 macrophages was 21.6 +/- 7.1 (standard error of the mean) at 1 h and increased to 59.0 +/- 16.4 at 8 h. Electron microscopy documented trophozoite destruction within macrophages. Association of G. lamblia with macrophages elicited an oxidative response; 50.9 +/- 3.6% of macrophages with trophozoites attached or ingested reduced the dye Nitro Blue Tetrazolium, compared with 13.0 +/- 5.2% for cells without associated trophozoites (P less than 0.04). These results demonstrate that macrophages are capable of ingesting G. lamblia in vitro and may play an important role in host defense in giardiasis.