Human hepatocellular carcinomas (HCC) were examined aromatase activity, an enzyme that converts androgen into estrogen. Such activity was detected in all 13 specimens of HCC (mean activity, 120 fmol/30 min/mg microsomal protein). The activity tended to be lower in the HCC tissue than in the surrounding liver tissue (mean activity, 230 fmol/30 min/mg microsomal protein), although it was higher in the HCC tissue from three of eight patients with Edmondson's Grade 2 disease. This relationship was not found in the five with Grade 3 disease. On the whole, aromatase activity was significantly higher in specimens from patients with Edmondson's Grade 2 tumors than in the less differentiated Grade 3 type (P < 0.05). These observations suggested that aromatase activity was present in human HCC and was related to the degree of histologic differentiation.