We analyzed 186 secretin provocation tests performed in our laboratory over a 5 year period. Positive tests, i.e., an increase in serum gastrin of more than 100 pg/ml, were found in 3 of 136 normogastrinemic and in 30 of 50 hypergastrinemic subjects. In all 16 patients with positive tests who were operated upon the diagnosis of gastrinoma was confirmed. In the 17 nonoperated patients the diagnosis of gastrinoma was supported by the demonstration of gastric acid hypersecretion. Two normogastrinemic patients with questionable gastrinoma had increases in serum gastrin of 72 and 73 pg/ml, respectively. Five patients with combined hypergastrinemia and basal hyperchlorhydria had negative secretin provocation tests: three had hypergastrinemia of antral origin, one had a gastrin-producing ovarian cystadenocarcinoma, and one had a pancreatic gastrinoma with liver metastases. We conclude that the secretin provocation test is helpful in the diagnosis of gastrinoma.