Epidermal growth factor (EGF) has documented trophic effects on several tissues, including small bowel (SB) mucosa. The purpose of this study was to determine the effect of EGF on intestinal adaptation after massive resection. Young Sprague-Dawley rats (weight, 154 +/- 8.6 g) underwent a 75% proximal SB resection, with primary reanastomosis, and were continuously infused with equivalent volumes of either saline or human recombinant EGF (6.25 micrograms/kg/h) via a subcutaneous osmotic pump. In other animals, the SB was transected and reanastomosed without resection and either saline or EGF was infused. The animals were allowed standard rat chow and water ad libitum and were killed after 28 days. SB was harvested and subjected to histological examination. Intestinal mucosa was analyzed for total DNA and protein contents. After massive SB resection, subcutaneous administration of EGF resulted in significantly increased animal weight (294.5 +/- 16 v 242.8 +/- 14g; P < .05), SB weight (52.8 +/- 7.0 v 37.2 +/- 6.0 cm; P < .05), SB length (14.0 +/- 1.3 v 7.4 +/- 1.6 g; P < .05), and mucosal thickness (1.04 +/- 0.2 v 0.68 +/- 0.2 mm; P < .05). DNA and protein analyses suggest that EGF may augment the mucosal hyperplasia response to massive SB resection. Administration of EGF after massive SB loss may be of nutritional benefit to the host through its enhancement of the normal postresection intestinal response.