The plasma concentration of neurotensin-like immunoreactivity (p-NTLI) was measured after oral intake of fat in (a) healthy non-obese volunteers, (b) grossly obese but otherwise healthy persons, and (c) patients who had undergone jejunoileal bypass because of gross obesity. In addition, p-NTLI was measured after intravenous infusion of fat in healthy non-obese volunteers. Basal p-NTLI levels were significantly higher in the patients with bypass than in the obese group. After oral intake of fat, the increase in p-NTLI was much greater and more sustained in the bypass group than in the two other groups. The type of bypass (end-to-end, end-to-side or biliointestinal) and the time after the operation did not correlate with the p-NTLI response. Intravenous infusion of fat evoked no increase in p-NTLI. To produce a rise in p-NTLI level, therefore, the fat does not have to be absorbed and hematogenously distributed to the N-cells (neurotensin-storing cells). This observation may suggest that direct contact between chyme and the N-cells, or local neural or hormonal factors, are required to stimulate release of NTLI. The authors suggest that increase in the postprandial release of neurotensin may promote the diarrhoea after bypass operations, and possibly has other physiologic effects in such patients.