A highly reproducible model of a solitary hepatic tumor in rats using ascites hepatoma AH13 has been developed using a two-step method which was suitable for quantitative chemotherapeutic studies. Diffuse hepatic metastases were induced first by inoculation of three different ascites hepatomas, AH13, AH130 and AH7974 into the portal vein in a dose-dependent fashion. Second, the induced hepatic tumor (3 x 10(7) cells) was minced into 1 x 1 x 4 mm fragments and implanted in the liver of normal rats. In this procedure, the AH13 strain proved best suited for the generation of a solitary hepatic tumor. The growth of the solitary liver tumor using AH13 was highly reproducible. To demonstrate the suitability of this solitary hepatic tumor model for the evaluation of chemotherapy, the tumor-burdened rats were treated with adriamycin (ADR) and mitomycin C (MMC). The reduction in tumor size was proportional to dosage, and the statistical significance of the differences between the treatment group and control group was proportional to dosage. A synergistic effect of ADR and MMC on the tumor also was demonstrated. This model should prove to be a useful tool for the testing of newly developed treatments of hepatic cancer.