(Gln4)-neurotensin was infused i.v. for 5 to 70 min at 3 different infusion rates (6, 12 and 18 pmol X kg-1 X min-1, respectively) in 19 male volunteers, aged 26-47. The plasma concentration of neurotensin-like immunoreactivity (NTLI), the lower esophageal sphincter (LES) pressure, blood pressure, heart rate. ECG and blood glucose concentration were measured. The volunteers did not report any subjective effects during the infusion. Following infusion periods of 30 min or more the volunteers often reported bowel movements starting 5 min or more after cessation of the infusion. Neither blood pressure nor heart rate changed significantly. No changes were noted in the continuous ECG or in the blood glucose concentration. Apparent steady state levels of about 300 pM NTLI were reached at about 40 min during infusion of 12 pmol X kg-1 X min-1 (Gln4)-neurotensin. In all volunteers the LES pressure was significantly reduced within 5 min of starting the infusion. In 6 volunteers 12 pmol X kg-1 X min-1 (Gln4)-neurotensin was infused i.v. for 5 min. The LES pressure decreased significantly (P less than 0.01) from 13.7 +/- 1.3 mmHg to 5.3 +/- 0.8 mmHg. The decrease in the LES pressure occurred at plasma NTLI concentrations of approximately 50 pM, i.e. at levels below those obtained in man after a meal or the ingestion of fat. The present data further support the hypothesis that in man plasma neurotensin, or a neurotensin metabolite is an endocrine hormone involved in the postprandial regulation of the motor functions of the gastrointestinal tract.