The retardation of gastric emptying induced by infusion of triglyceride into the small intestine is associated with suppression of antral pressure waves and stimulation of basal pyloric tone in combination with phasic pressure waves localized to the pylorus. The role of nitric oxide (NO) mechanisms in the control of pyloric motility was evaluated in 12 healthy male subjects (21-43 years), using the NO donor glyceryl trinitrate (GTN). Antropyloric pressures were measured with a manometric assembly incorporating nine sideholes, spanning the antrum and proximal duodenum, and a pyloric sleeve sensor. On separate days, an intraduodenal triglyceride infusion (10% intralipid at 1 mL min-1) was started during antral phase I activity and continued for 60 min. On one of the days GTN (600 micrograms) was given sublingually 20 min after start of the triglyceride infusion. The tonic pyloric motor response to triglyceride [5.6 (SEM 0.8,) vs. 2.7 (1.3) mmHg, P < 0.001] and both the number 3.2 (0.2) vs. 2.2 (0.2) min-1, P < 0.05] and amplitude [40 (4) vs. 27 (5) mmHg, P < 0.05] of phasic isolated pyloric pressure waves were reduced by GTN. These observations suggest that NO mechanisms are involved in the regulation of pyloric motor activity in humans.