Epidermal growth factor (EGF) is produced in the gastrointestinal tract and has been shown to have a transient stimulatory effect on mucosal growth and uptake of glutamine. This study investigated the delayed effects of EGF on mucosal brush-border membrane enzymes and glutamine uptake after extensive small bowel resection. Twenty-four New Zealand White rabbits underwent a 50% to 60% midjejunoileal enterectomy. One group of 12 had a subcutaneous osmotic pump inserted, delivering EGF at 0.3 microgram/kg/h for the first 7 postoperative days. The other group of 12 served as controls. Six rabbits from each group were killed at 3 weeks, and the remaining 12 were killed at 6 weeks. Six additional rabbits served asd nonsurgical controls. There was a twofold increase in mucosal dry weight at 3 weeks without EGF, and an almost fourfold increase with EGF, over control rabbits. This effect of EGF on the mucosa persisted for 6 weeks. Enzymatic activity per gram of protein in each group of rabbits was similar between the four groups of rabbits, although maltase activity increased approximately fourfold over that of nonoperative control animals. However, enzyme capacity of maltase and aminooligopeptidase (AOP) increased threefold and twofold (respectively) at 3 weeks without EGF, and sixfold and fourfold with EGF. Functional capacity is a measure of the load of nutrients that the intestine can digest and absorb, and therefore the derivable benefit to the animal. Glutamine uptake capacity increased 60% in 3 weeks without EGF, then declined by 6 weeks. However with EGF it increased 200% by 3 weeks, and further increased 400% by 6 weeks over control levels. The authors conclude that EGF markedly increases the functional capacity of the small intestine in rabbits that have undergone extensive small bowel resection; this effect persists for up to 6 weeks after a small initial dosage of EGF.