Intragastric titration, introduced in 1973, has become more popular than in the past and is being applied to the study of gastric secretion under a variety of conditions using NaHCO3 and NaOH as titrant. Physical chemical and technical considerations point to limitations on the conditions under which quantitative results can be obtained. At low end point pH, the limitation relates to volume expansion by secretions and titrant. Errors increase exponentially so that at pH 1.11 a 66% error is incurred and at pH 0.93 a 100% error would result. Neutralization with NaHCO3 poses limitations when CO2 is not effectively removed from the stomach, and even at pH 5.5 errors as large as 20% can be incurred. Errors increase markedly at high end point pH. Use of end point pHs above the pKa' of carbonic acid could lead to large amounts of factitious acid secretion i f the intralumenal contents are in equilibrium with CO2 entering from the gastric wall. There seems no reason that intragastric titration should not be a useful and quantitative method within the end point pH range of 4.0–4.5. In vivo validation of each experimental condition is needed. © 1979, American Gastroenterological Association. All rights reserved.