A dose response study of the effect on gastric acid secretion of synthetic human gastrin-17 (SHG) in doses of 50, 200, and 500 ng/kg/hr was performed in 8 healthy volunteers. The study was repeated on separate days during i.v. infusion of magnesium sulphate (0.4 meq Mg2+/kg/hr), of calcium gluconate (0.1 meq Ca2+/kg/hr) and of magnesium sulphate plus calcium gluconate. Magnesium infusion resulted in an increase in the dose of SHG required for one-half maximal secretion (D50), whereas infusion of calcium decreased D50. The difference in D50 of SHG when administered in combination with magnesium and with calcium was significant. Combined infusion of SHG, magnesium, and calcium resulted in the same D50 of SHG as found when SHG was infused alone. The calculated maximal acid response was almost identical in the four experiments except for a minor but nonsignificant decrease during calcium infusion. The results indicate an interaction of calcium, magnesium, and gastrin on parietal cell function and extend the observations of others in intact humans as well as in isolated gastric mucosa.