The transport of weak bases (pKa values 1.4 through 10.3) across in vitro and in vivo preparations of rat gastric mucosa have been compared. Asymmetric movements were observed in all cases, and the in vitro and in vivo data showed similar profiles of relation between the degrees of asymmetry and the pKa values of transported compounds. These profiles could be described by an equation based on a three-compartment model system, but it was necessary to postulate two such systems in parallel to give a satisfactory fit to the full range of pKa values tested. One system (I) is analogous to that described previously in small intestine. The properties of this system [(Pi/Pni)a = 2.5 x 10(-3), (Pi/Pni)b = 7.0 x 10(-1)] suggested that the intermediate compartment is a subepithelial extracellular compartment in which an alkaline pH is maintained [pHx = 8.5]. The second system (II) is the opposite polarity [(Pi/Pni)a = 1 x 10(0), (Pi/Pni)b = 3 x 10(-1)], and this system may be represented by the acidic lumen of the gastric tube [pHx = 2.0]. The principal differences between the in vivo and in vitro data could be ascribed to poor stirring of the luminal bulk phase in the in vivo situation. It was concluded that the determinants of weak base transport identified in studies with in vitro preparations are pertinent to the absorptive and secretory processes that occur in the intact stomach.