The aim of this work was to study in vivo the effect of ingestion of phosphopeptides (PP) alone or associated with caseinomacropeptide (CMP) on gastric secretion and to elucidate some possible mechanisms involved. Seven calves fitted with a gastric pouch received either a diet based on whey proteins without PP and CMP (C diet) or C diet in which PP or PP + CMP was introduced at concentrations similar to that of PP or PP + CMP in cow milk (PP diet and PP + CMP diet, respectively). Gastric juice secretion was measured during successive periods throughout the day. Twenty-four calves were fitted with a catheter introduced in one external jugular vein for blood sample collections. The daily secretion of electrolytes decreased with the presence of PP or PP + CMP in the diet. During the day, peptide supplementation in the diet resulted in (1) short term (1st-2nd postprandial h), a decrease of secreted quantities of gastric juice, enzymes and electrolytes, (2) long term (7-24 h after the morning meal), a decrease of electrolyte secretions. Intervention of gastrin, CCK, somatostatin and BPP could be probable. Globally, inhibition of gastric secretions seemed more important when PP was given in association with CMP in the diet rather than alone. CMP and PP may have short and long term action respectively over the 24 h day. To our knowledge, it is the first time that phosphopeptides coming from milk casein digestion are demonstrated to inhibit gastric secretion. Therapeutic uses are suggested. (C) 2009 Elsevier Inc. All rights reserved.