A prospective study of the value of secretin, calcium, and meal gastrin challenge tests for the diagnosis of gastrinoma indicated that the secretin test may be valuable. The calcium test was equally valuable, but it cannot be recommended as enthusiastically because it is time-consuming and may cause side effects. New criteria for interpretation of these tests were based on peak responses to the challenge. Further, the study revealed that patients with hypochlorhydria and hypergastrinemia could be identified without the use of gastric analysis. This prospective study reflects the current pattern of clinical practice at a referral institution where patients with gastrinoma, an unusual condition, are seen with regularity. The criteria we propose for interpretation of these tests are simple and could be applied to individual patients in whom a gastrinoma is suspected.