The knowledge of specific transport systems in cell membranes is helpful in understanding distribution processes of drugs and nutritions in the human body. In addition, specific transport systems allow drug targeting and the estimation of possible side effects of drugs. The present study was performed to investigate the transport of cationic drugs at cells representing the epithelia of the small intestine (Caco-2 cells) and the placenta (BeWo, JEG-3 and JAR cells). Furthermore, the participation of human organic cation transporters (hOCT) in the transport of the drugs was investigated. Several drugs inhibited apical uptake of the hOCT substrate [3H]MPP+ in Caco-2 cells and [3H]MPP+-flux across Caco-2 cell monolayers, the cationic drugs diphenhydramine and etilefrine were apically taken up in a saturable manner. For the first time, hOCT3 could be identified as the apical expressed MPP+ uptake system in Caco-2 cells. In the placental cell lines BeWo and JEG-3 a specific membrane potential dependent uptake system for the organic cation choline was characterized. hOCT were not involved in choline transport. The major part of the drugs interacted with the apical [3H]choline uptake system in BeWo and JEG-3 cells. [3H]Clonidine was taken up in JEG-3 cells in a saturable manner strongly pH-dependent, but Na+-independent. The uptake occured independently from the choline transport system and the hOCT. Quinine, quinidine, clonidine, diphenhydramine and guanabenz interacetd with the clonidine transport system.