The effect of cimetidine on gastric emptying and gastric secretion was evaluated in eight chair-adapted rhesus monkeys. A dye-dilution technique was used to simultaneously determine gastric emptying, gastric secretion of water and hydrogen ion (H+), and intragastric volume and H+ concentration. A continuous intravenous infusion of either saline (control) or cimetidine (4 mg X kg-1 X h-1) was administered during a 40-min fasting steady state and following intragastric instillation of 100 ml of water. During fasting, administration of cimetidine abolished H+ secretion and significantly decreased fractional emptying rate and water secretion (P less than 0.05). After the water load, cimetidine also suppressed H+ secretion and reduced fractional emptying and water secretion compared with control (P less than 0.05). Increasing HCl concentration of the test solution to 50 mM significantly decreased fractional emptying both during saline and further suppressed emptying during cimetidine infusion (P less than 0.05). In conclusion, cimetidine significantly decreased gastric emptying during fasting and following a liquid load. Restoring intragastric acidity to physiological levels removed the effect of gastric acid suppression on emptying and unmasked the full potential for cimetidine to decrease gastric emptying, possibily through an effect on gastric smooth muscle.