Systemic treatment with epidermal growth factor (EGF) induce growth of the large intestine. The aim of this study was to investigate the morphological properties early in the course of EGF- induced large intestinal growth. The effects of systemic EGF treatment on the morphological properties at the zero- stress state along the large intestine were investigated. EGF- treated rats and control rats were allocated into group with EGF treatment for 2, 4, 7, and 14 days (N = 6 for each EGF treatment group except N = 4 for the 14- day group). The controls had saline injected (N = 3 for each group). The excised large intestine was subdivided into four segments: the ascending colon, transverse colon, descending colon, and rectum. The length and weight of each segment was measured. The zero- stress state was obtained by cutting rings of the large intestine radially, and the opening angle was measued on video images. The thickness and cross- sectional area of the mucosa and muscle layers, and the inner and outer circumference were measured. The total colon length did not increase, whereas the weight of the large intestine, muscosal thickness and mass, and inner and outer circumference increased significantly ( P < 0:05). The increase was most prominent in the proximal colon after 7 days of EGF treatment. Later no further morphological changes were observed, except for a decrease in mucosal thickness in most segments and in mucosal cross- sectional area in the descending colon. In the controls and during the first week of EGF treatment, the opening angle was approximately 100 degrees. After 14 days the opening angle increased significantly in the ascending and transverse colon to approximately 172 and 135 degrees ( P < 0.05). In conclusion, this study demonstrates that systemic EGF treatment caused remodeling of the morphology of the zero- stress state in the large intestine in a time- dependent manner. The growth was most pronounced in the ascending and transverse colon and involved mainly the mucosal layer.