Numerous basic drugs have been reported to accumulate in the submaxillary gland. In this report an investigation of the nature of this uptake process is described using the basic drugs Ba 31531 {4-[5-amino-3-(4-pyridyl-1-pyrazolyl)-1-methylpiperidine] and ST-155 [2-(2,6-dichloroanilino)-2-imidazoline HCl)]}. These compounds are reversibly taken up into the gland by a process with a high capacity which could be reproduced in vitro with tissue slices. The uptake into tissue slices exhibited a pH dependency which suggested that the accumulation was the result of a low intracellular pH. However, the intracellular pH determined with DMO was too high to account for this uptake. Attempts to account for the uptake by nonspecific binding to tissue components in homogenates also failed, suggesting that the uptake process requires an intact cell. © 1969.