We have investigated the effect of the weak base Tris on the processing and secretion of albumin and α-1 antitrypsin by hepatocytes in culture. We show that the secretion of both proteins is 90% inhibited by 30 mM Tris. The post-synthetic processing of both proteins is inhibited to the same extent. These effects are completely reversible. Cell fractionation indicates that albumin accumulates in the Golgi, whereas α-1 antitrypsin fails to leave the endoplasmic reticulum.