Objective: Nitric oxide (NO) mechanisms have been shown to modulate fasting small intestinal motility in humans, but a role in the regulation of human postprandial small intestinal motility has not been assessed. The aim of this study was to evaluate the effect of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) on the regulation of small intestinal nutrient transit and postprandial small intestinal motility in healthy humans. Material and methods: Seven healthy male volunteers (18–27 years) underwent antroduodenal manometry recordings for 4 h on 2 occasions after intraduodenal instillation of a 500 KJ [120 Kcal] test meal. The meal was administered 15 min after the commencement of a 60-min intravenous infusion of l-NMMA (4 mg kg−1 h−1) or saline (0.9%). Studies were separated, performed in randomized order and >3 days apart. The frequency and amplitude of duodenal pressure waves together with time to return of fasting motility (phase III) was determined. On each day, small intestinal transit was measured using a lactulose breath test. Results: The test meal interrupted fasting small intestinal motility in all subjects. The time to recurrence of fasting motility following its postprandial disruption was similar (l-NMMA versus saline 1.6±0.2 h versus 1.9±0.1 h; p>0.05). Duodenocaecal transit was delayed by infusion of l-NMMA compared with saline (l-NMMA versus saline 92.1±3.9 min versus 66.4±6.4 min; p