The intravenous secretin test is widely used to distinguish gastrinoma (Zollinger-Ellison syndrome) from other causes of fasting hypergastrinemia. We report 2 patients with fasting hypergastrinemia and a rise of greater than 200 pg/ml in serum gastrin concentration after intravenous injection of 2 CU/kg body wt of pure natural secretin. Both patients had pentagastrin-fast achlorhydria. Thus, the intravenous secretin test may be positive in patients with achlorhydria-related hypergastrinemia. Gastric acid secretion should be measured in hypergastrinemic patients before embarking on a secretin test.