The in vitro interaction of neutrophils and virulent axenic Entamoeba histolytica trophozoites on Chang liver cells was studied to determine if the presence of neutrophils enhanced destruction of liver cell monolayers. Axenic amoebae (strain HM1:IMSS) destroy liver cell monolayers in a dose-dependent manner (P less than .001). Human neutrophils had no effect on the liver cell monolayers; however, when neutrophils were added to amoebae, destruction of monolayers was enhanced (P less than .05 compared with amoebae alone). Similar results were obtained when Chinese hamster ovary (CHO) cells were substituted for Chang cells (P less than .01). In this in vitro model, neutrophils were lysed by amoebae, as determined by release of 111Indium oxine from labeled neutrophils (P less than .001). The augmentation of cytopathogenicity for Chang cells was not inhibited by catalase (3,000 U/ml) and was observed with neutrophils from a patient with chronic granulomatous disease. N-Acetyl-D-galactosamine (45.0 mM) decreased monolayer destruction due to amoebae, with or without the presence of neutrophils (P less than .01). These studies establish that in vitro lysis of human neutrophils by E. histolytica enhances destruction of liver or CHO cell monolayers and that this effect is not due to release of neutrophil oxidative products.