The uptake mechanisms of organic cations such as tryptamine, tyramine, 5-benzyloxytryptamine (BOTA) and their zwitterionic derivatives (tyrosine, tryptophan, 5-benzyloxytryptophan (BOTP)) by rat intestinal brush-border membrane vesicles and liposome containing phosphatidylserine were studied and compared. As compared to their zwitterionic derivatives, uptake rates by rat intestinal brush-border membrane of these three cations were far superior. The binding of cationic compounds to the brush-border membrane was also higher than those of their zwitterionic derivatives. Furthermore, the binding behaviour of BOTA and tryptamine to phospholipid liposome clearly amplified with increasing amounts of phosphatidylserine. In contrast, the contents of phosphatidylserine, a negatively charged phospholipid, exhibited no effects on the binding of zwitterionic derivatives (tryptophan and BOTP). The double-reciprocal plot of tryptamine binding with BOTA to liposome showed competitive inhibition. These results suggest that the binding of organic cations to the membrane lipid has a relatively high specificity despite the absence of membrane protein such as a transport-carrier in the liposome, and that the binding of cationic compounds play an important role in the uptake to the cell membrane systems.