The continuous rat hepatoma cell line H4IIEC3/G- and rat hepatocyte primary cultures (hpc) were compared with regard to their capacity to metabolize structurally different promutagens. The sensitivities of both activation systems were evaluated by comparing the induction of SCE in H4IIEC3/G- cells themselves with that ih V79 cells co-cultured with hpc. Of the six chemicals tested, aflatoxin B1 (AFB1), cyclophosphamide, dimethylnitrosamine and nitrosomorpholine (NM) were shown to be inducers of SCE in H4IIEC3/G- cells as well as in V79 cells with hepatocyte activation. 7,12-Dimethylbenzanthracene gave positive responses in hpc/V79 co-cultures but not in H4IIEC3/G- cells whereas benzo[a]pyrene was negative in both systems. These results suggest that H4IIEC3/G- cells retain metabolic activities to convert different indirect mutagens into their active forms and clearly indicate the presence of liver specific cytochrome P-450-dependent mono-oxygenases. However, freshly isolated hepatocytes are more efficient in metabolizing the test compounds. Although hpc provide only external activation, the V79 cells system appears to be more sensitive for the detection of promutagens.