It is unknown whether the gastrin response to secretin (secretin test) can distinguish hypergastrinemia due to vagotomy from hypergastrinemia due to Zollinger-Ellison syndrome (ZES). Therefore, we measured serum gastrin concentrations basally and in response to intravenous secretin in 13 vagotomized duodenal ulcer patients without preoperative evidence evidence of ZES and in 5 vagotomized patients with ZES. Following secretin, serum gastrin concentrations increased 40 pg/ml or less [mean (+/- SE) rise 23 +/- 3 pg/ml] in the vagotomized patients without ZES. On the other hand, in the patients with ZES serum gastrin increments after secretin ranged from 105 to 1224 pg/ml. Thus, a large (> 100 pg/ml) rise in serum gastrin concentrations following secretin in a vagotomized patient should suggest Zollinger-Ellison syndrome and not be attributed to vagotomy per se.