In this study, the effects of IFN gamma, TNF alpha and EGF on the expression of HLA class I antigen and the proliferation of human hepatocellular carcinoma-HepG2 cells were investigated. In response to IFN gamma or TNF alpha stimulation, the expression of HLA class I mRNA in HepG2 cells was increased by 2-4 fold. Cell surface HLA class I antigen was also increased, but in comparison, the increase was not as high as HLA class I mRNA expression. This is probably due to the limitation of protein translational and post-translational processing. The enhancing effect of EGF on cell surface HLA class I antigen could be noted but was not very significant. IFN gamma and TNF alpha could also inhibit the proliferation of HepG2 cells. Interestingly, the effect of EGF on the proliferation of HepG2 cells depended on its concentration. At low concentrations, EGF increased cell proliferation in terms of thymidine incorporation. However, if the concentration of EGF was relatively high, it could also exert an inhibitory effect on thymidine incorporation into HepG2 cells. The remarkable morphological alteration was observed when HepG2 cells were exposed to EGF at concentrations higher than 5 ng/ml. This morphological alteration might be associated with the inhibitory effect of EGF at high concentrations on the proliferation of HepG2 cells.