The effect of nitroglycerin and long-acting nitrates in normal humans is unknown. Therefore, we studied the effect of commonly used clinical doses of nitrate preparations on the esophagus in normal subjects. Three minutes after administration of sublingual nitroglycerin 0.6 mg, a significant reduction in lower esophogeal sphincter pressure occurred (19.0 +/- 2.6 to 12.7 +/- 2.2 mmHg (P < 0.01). This effect was transient, and no effect was seen on amplitude, duration of esophageal contractions or peristaltic wave velocity measured 6 min after nitroglycerin administration. Neither nitroglycerin ointment, 1.5 in. applied to the forearm, nor 20 mg oral isosorbide dinitrate, resulted in a major change in any measured parameter of esophageal motility. In addition, pretreatment with long-acting nitrates did not alter lower esophageal sphincter response to intravenous pentagastrin.