Androgen receptors (AR) in the cytosol of hepatocellular carcinoma (HCC) were assayed in 45 unselected patients in whom radical hepatic resection was performed. Thirty-one patients had detectable amounts of ARs in tumors, ranging from 2.3 to 82.6 fmol/mg protein with the dissociation constants (Kd) of 4.1-30.9 x 10 (-10) M. The receptor was not found in the remaining 14 cases. AR negative HCCs were significantly more common among women and nonalcoholic patients. Otherwise, there were no significant difference in the clinicopathologic background between patients with AR positive HCCs and those with AR negative tumors. Three patients died of liver failure in the former group, whereas two died in the latter; one patient died of liver failure and the other died of pneumonia (results were not statistically significant). Excluding those five operative deaths, the recurrence rates were 67.9% in the group of patients with AR positive HCCs and 33.3% in the group of patients with AR negative tumors (0.1 less than p less than 0.05). The 5-year survival rate was significantly better (p less than 0.05) in patients with AR negative HCCs (62.2%) than in those with the positive tumors (17.3%). In light of the current results and previous experimental works by others, it is likely that testosterones enhance the growth and invasiveness of human HCC, which is mediated by AR in the tumor.