It is generally agreed that the adaptive response in the residual bowel after major intestinal resection is dependent on luminal nutrition and pancreaticobiliary secretions. Recent evidence, however, suggests that humoral mechanisms, e.g., gastric or enteroglucagon, may also play a part in this process. A 75% proximal small bowel exclusion was performed in 16 male Wistar rats and the excluded bowel was fashioned into a Thirty-Vella fistula. Half of the animals were allowed food ad libitum, while the rest were fed i.v. The animals were killed at 12 days, and plasma gastrin and enteroglucagon were measured, while cell proliferation was determined by measuring the crypt cell production rate employing a stathmokinetic method using vincristine and crypt microdissection. In addition to these animals, 16 rats had a jejunal transection only, with half of these animals nourished i.v., while the remainder were allowed food ad libitum. In the Thirty-Vella rats, plasma enteroglucagon was greater with oral feeding (566 .+-. 59 pmol/l) than with i.v. feeding (120 .+-. 42 pmol/l) (P < 0.01), but gastrin levels did not differ in the 2 groups. In the ileum in continuity, crypt cell production rate/h was greater in the orally fed animals (52 .+-. 8) compared with the i.v. fed group (18 .+-. 5) (P < 0.001). In the excluded fistula, crypt cell production rate/h was reduced 23.8 .+-. 2 in orally fed rats, but this was greater than in the i.v. fed group (16 .+-. 1.5) (P < 0.01). Both orally and i.v. fed transected rats had significantly lower plasma hormone levels, and reduced crypt cell production rate compared with the respective Thirty-Vella groups. A distinct role for a humoral agent responsible for the proliferative changes seen after small bowel resection is suggested and in this respect enteroglucagon appears more relevant than gastrin.