Although in acute intestinal amoebiasis the events occurring during the initial interaction of Entamoeba histolytica trophozoites with the mucosa of the large intestine probably determine the invasion by the parasites, an appropriate experimental model to study them does not exist. To develop such a model we used rabbit colonic segments (0.28 cm2) mounted in Ussing-type chambers. These preparations had electrophysiological properties (potential difference, short-circuit current, and electrical resistance) similar in magnitude and duration to those reported for stripped colonic mucosa. Lysates from 50,000 Entamoeba invadens PZ strain trophozoites (virulent to reptiles) added to the mucosal side of preparations had no effect, whereas lysates from the same number of E. histolytica HM1 strain trophozoites (virulent to humans) caused an immediate decay of electrophysiological properties. E. histolytica lysates induced the formation of translucent vacuoles at the bases of epithelial cells and separation between the epithelium and the lamina propria. The specificity and speed of the electrophysiologic effects of E. histolytica lysates and their correlation with the microscopic lesions suggest that this model may be useful to analyze the initial pathogenic events of intestinal amoebiasis.