The effect of (Gln4)-neurotensin on the motor activities of the duodenum and small proximal jejunum was investigated in 8 healthy volunteers who fasted for at least 8 h. Motor activity was monitored by measuring the intraluminal pressure at three levels. The proximal site for pressure recording was in the first part of the duodenum, the middle was at the angle of Treitz, and the distal was 25 cm further down. Under control conditions the median time between the migrating motility complexes was 106.3 min. (Gln4)(-Neurotensin, 3 or 6 pmol/kg . min, infused intravenously for 200 min inhibited the migrating motor complexes for 220.4 min (median time) and they were replaced by irregular pressure waves with a frequency of 4-7 waves/min. The plasma concentration of neurotensinlike immunoreactivity increased from 13 +/- 2.8 pM to 131 +/- 6 pM and 231 +/- 16 pM, respectively. Ingestion of fat (55 ml 20% Intralipid) inhibited the migrating motor complex for 196.1 min (median time) and the migrating motor complexes were replaced by irregular pressure waves. The data show that (Gln4)-neurotensin alters the motility pattern in the duodenum and proximal jejunum in man from a fasting- to a fed-type. They further support the contention that neurotensin may function as an endocrine hormone participating in the postprandial regulation of intestinal motility.