An oral optimum therapeutic dose of poldine was established in 5 normal subjects. Acid secretion in response to a protein meal was measured for 3 hr by continuous intragastric titration with sodium bicarbonate. Poldine 30 min before the meal reduced food-stimulated acid secretion from zero to 60% in the 5 subjects (average inhibition 32%). Poldine inhibited histamine-stimulated acid secretion to approximately the same extent. In separate experiments, gastric acidity after the meal was allowed to seek its natural level (i.e., there was notitration with bicarbonate). Poldine reduced average hydrogen concentration of the gastric contents by 85 to 50% from 1.5 to 3 hr after the meal. Since poldine did not alter the volume or the buffer content of the stomach, poldine inhibition of gastric acidity is due entirely to reduction of acid secretion and not to delayed emptying of food buffer. Poldine had no consistent effect on serum gastrin concentration after the meal when pH was maintained at a constant level by titration with bicarbonate; therefore, poldine inhibition of acid secretion is not mediated by a reduction of serum gastrin concentration.