Hepatic stellate (HS) cells were isolated from the livers of metallothionein (MT)-null and control mice and used to establish IMS/MT(-) and IMS/N cell lines, respectively, using SV40 virus transformation. Cellular morphology, incorporation of vitamin A and expression of alpha-SMA, desmin and SV40 T-antigen were used to confirm that both cell lines were immortal HS cells. The growth rates of both cell lines were similar and there was little difference between cell line sensitivity to zinc. MT-null IMS/MT(-) cells were more sensitive to cadmium and mercury, although both cell lines accumulated almost equal amounts of cadmium during a 24-hr culture period. As HS cells play an important role in hepatic fibrosis and are activated by heavy metals such as cadmium or reactive oxygen, the MT-null HS cell line derived in this study should be a useful experimental model for examination of the role of MT in HS cell activation.