Stem cells have unique properties such as self-renewal, plasticity to generate various cell types, and availability of cells of human origin. The characteristics are attentive in the toxicity screening against chemical toxicants. Placenta-derived stem cells (PDSCs) have been spotlighted as a new cell source in stem cell research recently because they are characterized by their capacity to differentiate into multilineages. However, the use of PDSCs as an in vitro screening model for potential drug candidates has not yet been studied. Here, we analyzed the potentials for bone-marrow-derived mesenchymal stem (BM-MSCs), which is a representative adult stem cells and PDSCs as an in vitro hepatotoxicity screening system, using well-known hepatotoxicants. BM-MSCs and PDSCs were analyzed to the potential for hepatogenic differentiation and were cultured with different concentrations of hepatotoxicants for time courses. The viability and ATP-binding cassette (ABC) transporters were measured by the MTT assay and RT-PCR, respectively. The sensitivities of PDSCs to hepatotoxicants are more sensitive than those of BM-MSCs. The viability (IC(50)) to in PDSCs was less than that of BM-MSCs after 48 and 72 h (P < 0.05) of CCl(4) exposure. The toxicities of CCl(4) were decreased by fourfold in hepatogenic differentiation inducing PDSCs compared to the undifferentiated cells. The alteration of ABCGs was observed in PDSCs during differentiation. These findings suggest that the naïve PDSCs expressing ABCGs can be used as a source for in vitro screening system as well as the expression patterns of ABCG1 and ABCG2 might be involved in the sensitivity of PDSCs to hepatotoxicants.