Hepatocellular carcinoma (HCC) in human and murine has been known to occur more frequently in male than female. Attempts have been made to find a possible mechanism of increased growth advantage in the HCC cells by testosterone (T). Treatment of HepG2 human HCC cells with T increased DNA synthesis by 30-50%, whereas T increased it by 10-30% in FaO (rat) cells. Androgen receptor (AR) levels in HepG2 and FaO cells were 94.1 fmol/mg protein and 55.0 fmol/mg protein, respectively. Expression of AR mRNA species was detected as about 10 kb (doublet) in HepG2. On the other hand, much less expression of AR mRNA was observed in FaO cells. AR signals around 28S rRNA (4.7 kb) and the small size RNAs detected in the total cellular RNAs were not found in the poly(A) + RNAs isolated from the cells. Contrary to the earlier observation by other investigators, expression of hepatic AR was not down-regulated by T until 72 h of treatment. These results demonstrate one of the modes of action by T for the preferential development of HCC in male.