In healthy controls (n = 7), patients with duodenal ulcer (n = 7), primary hyperparathyroidism (n = 7), and 1 case of excluded gastric antrum the effects of intravenous secretin ("Karolinska"; 3 U/kg/h for 90 min) upon serum calcium fractions, total protein, and the integrated response of gastrin and glucagon were investigated. In all groups total calcium, total protein, and protein-bound calcium fraction rose significantly but the inonized calcium fraction remained stable. Since serum concentration of gastrin and glucagon could not be altered in any of the groups a direct interference of these hormones with calcium homeostasis during secretin infusion can be ruled out. Hyperparathyroid patients had higher baseline glucagon values (209 +/- 30 pg/ml) than normals (127 +/- 6 pg/ml) and ulcer patients (138 +/- 11 pg/ml) and maintained a higher hormone output throughout the experiment. Together with data on the patient with excluded antral parts it is concluded that the hypercalcemic effect of secretin is not mediated by calcium-regulating hormones but must be of an unspecific nature.