An established epithelial cell line (A6) from toad kidney was used to study in vitro cytotoxicity. When grown on permeable support, A6 cells form a monolayer epithelium with a high electrical resistance and a transepithehal potential. These two easily measured electrophysiological endpoints showed a dow-related decrease after exposure of the cells for 24 hr to 21 selected chemicals. It was demonstrated that both transepithelial potential and transepithelial resistance correlated well with acute cytotoxicity data obtained using human lymphocytes and with calculated human lethal dose values. The polarity of the epithelial cells was demonstrated by specific chemicals that targeted the basolateral membrane. The results show that electrophysiological measurements of A6 epithelia could be used as a general cell model to study cytotoxicity and as a specific model to evaluate toxic affects on tight epithelia.