Basal lower esophageal sphincter (LES) pressure was measured in 6 patients with the Zollinger-Ellison syndrome (ZES) and hypergastrinemia, and in 6 patients with duodenal ulcer and normogastrinemia. Basal LES pressure in ZES patients, 17.0 +/- 3.7 (mean +/- SE) mm Hg was similar to basal LES pressure in duodenal ulcer patients, 18.3 +/- 3.5 mm Hg (P greater than 0.10). LES pressure and serum gastrin concentration were not related in the ZES patients, r = 0.03, or in the duodenal ulcer patients, r = 0.20. Intravenous infusion of calcium gluconate in ZES patients produced a marked rise in serum gastrin concentration, delta = 1580 +/- 1110 pg per ml (P less than 0.001), and a moderate but significant rise in LES pressure, delta = 5.9 +/- 0.9 mm Hg (P less than 0.05). In duodenal ulcer patients calcium infusion produced only slight rises in gastrin concentration, delta = 10 +/- 12 pg per ml, and LES pressure, delta = 2.1 +/- 0.5 mm Hg, which were not significant (P greater than 0.10). This study suggests that basal LES pressure is not regulated by blood gastrin levels in the ZES. We interpret the calcium infusion study to show that the LES pressure in patients with ZES may respond to acute changes in endogenous gastrin levels.