Liquid elemental diets (ED) will, in time, cause atrophy of the gut. Pentagastrin (PG), neurotensin (NT), and bombesin (BBS) are peptides that have trophic effects on the gut of normal rats. This study examined the effect of these three agents on gut atrophy produced by ED. Four groups of rats were given an ED and injected with either saline (control), PG (250 micrograms/kg), NT (300 micrograms/kg), or BBS (10 micrograms/kg) subcutaneously every 8 hours for 5 or 10 days. A fifth group was fed rat chow ad libidum. The rats were killed on day 6 or 11; the pancreas and segments of small intestine were removed. Atrophy of ileal mucosa was apparent on days 6 and 11, and atrophy of jejunal mucosa was manifest by day 11. Bombesin prevented jejunal mucosal atrophy and significantly increased ileal mucosal growth (compared with control). Neurotensin prevented the jejunal, but not the ileal, mucosal atrophy produced by ED. Pentagastrin had no effect on gut mucosa. Bombesin and PG, but not NT, stimulated pancreatic growth. Neurotensin stimulates pancreaticobiliary secretions (PBS), which are known to stimulate gut growth. Jejunoileal bypass was performed to determine whether trophic effects of NT on gut mucosa were mediated through stimulation of PBS. After 1 week treatment, animals were killed and segments of intestine removed. As expected NT was trophic for gut mucosa in continuity with the luminal stream; furthermore NT produced significant stimulation of growth of gut mucosa in the bypassed segment. We conclude that both BBS and NT are trophic for intestinal mucosa of rats given ED; both agents have a more pronounced effect on jejunum. The trophic effect of NT is mediated, in part, by a mechanism unrelated to stimulation of PBS. Bombesin and NT may have important regulatory functions in the adaptive growth of small bowel mucosa and in the maintenance of gut mucosal integrity.