The histological abnormalities of amoebic colitis have been well described but their evolution over a period of time has not been clearly examined. To study this, three- to four-week-old guinea-pigs were inoculated intracaecally with 80,000 to 100,000 Entamoeba histolytica trophozoites, left untreated and killed at 3, 5, 8, 11, 14 and 21 days, when the caecum was removed and the tissue sectioned and stained with H & E and PAS. Although there was considerable variation in the type of histological abnormality seen on different days of the experiment, there was a definite pattern of evolution. Initially there was diffuse infiltration of the lamina propria by lymphomononuclear cells in the presence of an intact surface epithelial lining. This was followed firstly by superficial and then by deep ulceration of the mucosa. Mucosal invasion by the trophozoites was seen only at this stage and was accompanied by tissue necrosis; the most severe abnormalities occurred on day 11. The final development was regenerative activity which was first noted on day 11, and became more prominent subsequently. The presence of cellular infiltrate in the lamina propria in the absence of trophozoites and damage to the surface epithelium, suggests that these abnormalities are not the direct effect of amoebae. It is suggested that the initial damage is caused by an enterotoxin; the trophozoites enter the mucosa only when there is a break in the surface epithelium. Once within the tissues, trophozoites aggravate the damage by their ability to phagocytose and to release cytotoxic enzymes.