Human peripheral blood monocytes were purified by adherence on microexudate-coated plastic and detached by exposure to 1 mM ethylenediamine tetracetic acid. Lysis of Trichomonas vaginalis was measured as release of 3H-thymidine from prelabelled protozoa after 48 hr of incubation. Human blood monocytes had appreciable levels of spontaneous cytotoxicity against Trichomonas vaginalis at effector-to-target cell ratios ranging from 3:1 to 25:1. Cytotoxicity was expressed with fetal bovine serum and human AB serum. Unseparated mononuclear cells, containing 10-25% monocytes as assessed by staining with non-specific esterase, were significantly cytotoxic against Trichomonas vaginalis but cytolysis levels were lower than those of purified monocytes. Lymphoid cells depleted of adherent cells by repeated incubations on plastic (less than 2% esterase-positive cells) had little cytotoxicity against these protozoa. In vitro exposure to silica natural 40-75% inhibition of the cytotoxic capacity of monocytic preparations. The natural cytotoxic capacity of human monocytes against Trichomonas vaginalis could represent one line of resistance against these protozoa.