Patients referred to us with "positive" secretin tests and the diagnosis of Zollinger-Ellison syndrome were found to be achlorhydric. This observation led us to study prospectively the accuracy and precision of serum gastrin determinations from commercial laboratories. Synthetic gastrin (G17) was added to serum to achieve gastrin concentrations of 50, 100, 250, 500, 750, 1000, 3000, and 5000 pg/mL after subtraction of the basal value (24 pg/mL). Three aliquots of each concentration were analyzed by radioimmunoassay in our laboratory (Health Science Center at Brooklyn) and sent to four major commercial laboratories that perform 5000 to 25,000 gastrin assays per year. The reported gastrin concentrations of the triplicate samples demonstrate that many commercial laboratories failed to accurately measure gastrin. Commercial laboratories generally reported higher-than-actual gastrin concentrations in samples containing less than 500 pg/mL and lower-than-actual gastrin concentrations in samples containing more than 500 pg/mL. Of all aliquots containing 100 pg/mL or less, 14 of 24 samples (58%) were reported by commercial laboratories to contain elevated gastrin concentrations. At gastrin concentrations from 250 to 5000 pg/mL, the range of values (highest- to lowest-reported value for each concentration) was greater than 200 pg/mL in 62% of triplicate samples reported by commercial laboratories. These data indicate that determinations by some commercial laboratories lack the precision required to satisfy the current diagnostic criterion (a postsecretin rise from basal gastrin of 200 pg/mL or greater) for Zollinger-Ellison syndrome. Clinicians should be aware of this problem and obtain more basal serum gastrin samples to allow for an analysis of the range of baseline values prior to secretin injection.