Intestinal amebiasis is still an important health problem in developing regions of the world. In order to advance our knowledge on the pathogenesis and to test the relevance of recently obtained in vitro observations, suitable in vivo experimental models of intestinal amebiasis are needed. In the past a variety of laboratory animals have been used, but the mouse, whose genetics and immunology is well known, has been seldomly used. Therefore, Entamoeba histolytica strain HM1:IMSS was directly inoculated into the cecum of C3H/HeJ mice, which were sacrificed at 5, 10, 15, 20, 25 and 30 days for histopathologic analysis. An ulcerative inflammatory disease highly reminiscent of human amebiasis was observed. Early 5 day lesions consisted of tiny erosions of the surface epithelium which evolved to deeper and more extensive destructive lesions of the cecal wall. Indeed, flask-shaped ulcers, intestinal perforations and intramural abscess formation were observed at later times. It was noticeable that, despite the lack of obvious significant tissue invasion by amebae, ulcerative disease was extensive and found virtually in all mice. These observations support the view that tissue invasion by trophozoites is not necessarily required for ulcerative disease to occur, suggesting a role for toxic factors released by amebae.