The relationship of tumor volume doubling time to length of patient survival was investigated for 15 patients with small hepatocellular carcinoma smaller than 4.5 cm in diameter. The mean tumor volume doubling time of these 15 nodules was 102 +/- 77 days (mean +/- SD; range 41 to 305 days) before the initiation of a specific treatment for cancer. These doubling times tended to correlate with mitotic indexes of the tumors and the patients could be divided into two groups according to the therapeutic modalities used. Patients in Group A received systemic chemotherapy without response or nonspecific treatments for cancer. In this group, there was a positive correlation between tumor volume doubling time and survival length (r = 0.8812; P less than 0.025). Patients in Group B either received hepatectomy after transarterial embolization or systemic chemotherapy or received hepatectomy alone. In this group, early death occurred in patients who had shorter tumor volume doubling times. Three surgically treated patients in Group B were evaluated as having survived for a significantly long period as assessed from their tumor volume doubling times. These results indicate that tumor volume doubling time is one of the determining factors of survival length in patients with hepatocellular carcinoma, and, therefore, can be used in the evaluation of therapeutic efficacy.