The ability of spleen, mesenteric lymph node (MLN) and peritoneal exudate (PEC) cells from susceptible (A/J) and resistant (B10.A) mice to kill trophozoites in vitro was determined. Both duration of incubation and cell density influenced giardicidal activity. Maximal killing was observed after 6 hr of incubation at the effector to target ratios of 30:1 and 50:1. Cells isolated from A/J and B10.A mice during the elimination phase of the infection killed more trophozoites than those isolated from mice during the acute phase of the infection. Cells isolated from mucosal sites (MLN) of donors infected for 15 days killed more trophozoites in vitro than those isolated from systemic sites (spleen, PEC). There were no differences in the giardicidal activity of cells from susceptible and resistant mice. Killing of trophozoites was mediated by plastic-adherent cells with macrophage properties. Non-specific stimulation with thioglycollate and the presence of immune mouse serum enhanced the capacity of macrophages to kill parasites. There was no apparent relationship between the capacity of A/J and B10.A mice to mount cell-mediated effector responses and their ability to control the infection with Giardia muris.