Various criteria based upon study of basal acid and pepsin gastric secretion have been proposed to facilitate the diagnosis of Zollinger-Ellison (ZE) syndrome. These criteria have been analyzed on 599 gastric secretory studies on subjects who had undergone no gastric surgery. This population included 20 ZE syndromes and 495 duodenal ulcers (DU). Neither an acid concentration > 100 mEq/l nor an acid output > 15 mEq/h is sufficiently discriminatory for the diagnosis of ZE syndrome when taken alone because they were found in 8.2 and 6% of DU, respectively. However, the association of these two criteria in the same secretory study strongly increases the suspicion of this diagnosis because it was found in 60% of ZE syndrome cases and in only 2.8% of DU. A valuable modification of those criteria taken alone is the presence of a basal acid output > 18 mEq/h. In the present series, however, the most interesting criterion has proved to be a pepsin/acid correlation (K 25) equal to or lower than 35. In any case, a low pepsin/ acid correlation improves the suspicion of the diagnosis. The most characteristic secretory status of the ZE syndrome consists of an association of a basal acid output > 18 mEq/h, a basal acid concentration > 100 mEq/l and a K 25 < 35 which is found in 55% of ZE syndrome cases and in only 0.6% of DU without pyloric stenosis. These criteria have to be considered as a means of selection of patients in whom radioimmunoassay of serum gastrin is needed.