Epidermal growth factor (EGF) was administered by chronic subcutaneous or intracolonic infusion into normal adult rats to determine the effect on colonic growth. Subcutaneous infusion of 200 micrograms EGF/kg/day for 7 days increased the cross-sectional mass and protein content of the muscularis and mucosal layers of the proximal colon, with the distal colon showing less response. In the mucosa, subcutaneous EGF induced proportional increments in the number of cells per crypt, and in the number of cells positively labelled for PCNA, while maintaining a normal crypt growth fraction. In contrast, an 8-fold higher dose of EGF administered intraluminally had no effect on colonic mucosal or muscularis growth. This lack of bioactivity was unlikely to reflect rapid luminal degradation as radiolabelled EGF remained stable in the colonic lumen for at least 4 h. The results demonstrate that the normal adult colon is responsive to subcutaneously delivered EGF, particularly the proximal colon, whereas EGF may not be active on the normal colon when presented from the luminal direction.