BACKGROUND Octreotide (SMS) is a somatostatin analogue utilized in patients with short bowel syndrome (SBS) to decrease output. It may inhibit small bowel adaptation by blocking the secretion of trophic hormones such as epidermal growth factor (EGF). This study delineates the effects of SMS and EGF on nutrient transport in SBS. METHODS One week after 70% jejunoileal resection, 20 New Zealand White rabbits (2 kg) received subcutaneous infusions of saline or EGF (1.5 micrograms/kg/hr) and injections of saline or SMS s.q.b.i.d. The study groups were EGF/saline, saline/saline, saline/SMS, and EGF/SMS. After 7 days of infusion, intestinal brush border membrane vesicles were prepared and nutrient transport measured. RESULTS SMS reduced active nutrient transport. Kinetics confirmed this was secondary to a reduction in functional carriers in the brush border membrane, without a change in carrier affinity. The coinfusion of EGF ameliorated this effect. On an individual basis, EGF alone did not significantly increase nutrient transport, but when taken as a group, nutrients transport was upregulated 26%. CONCLUSIONS SMS is detrimental to small bowel adaptation. EGF reverses this effect and may benefit patients with SBS who require SMS to control high intestinal output.