Inhibitory nitrergic neurons are known to play a role in the regulation of motility patterns of the distal esophagus, the lower esophageal sphincter (LES), and the gallbladder. Our study aim was to investigate the effects of "long-term" (i.e., prolonged) oral intake of L-arginine (L-Arg), the endogenous source for nitric oxide (NO) synthesis, on postprandial LES pressure (LESP), esophageal motility, gastroesophageal reflux, and gallbladder motility. L-Arg (30 g/day) or glycine (placebo; 13 g/day; isosmolar) was given orally to 10 healthy male volunteers for 8 days, according to a randomized, crossover design. Twenty-four-hour urinary nitrite/nitrate excretion was measured to indicate NO synthesis. Basal early postprandial LESP was lower after L-Arg ingestion (2.2 kPa) than after glycine ingestion (2.7 kPa) (P < 0.05). L-Arg abolished the physiological late postprandial rise in LESP. Transient LES relaxations were longer lasting after L-Arg ingestion (P < 0.02). Esophageal motility and reflux were not affected (not significant). Fasting and residual gallbladder volumes were greater after L-Arg ingestion (P < 0.05). Urinary nitrite/nitrate excretion was higher after L-Arg intake (P < 0.05). In conclusion, long-term oral L-Arg suppresses late postprandial LESP increase, prolongs transient LES relaxations, and increases fasting and residual gallbladder volumes. These effects may be mediated by increased NO synthesis.