Twenty-two patients with adenocarcinoma metastatic to the liver were treated with rapid fractionation whole-liver irradiation (1350-2100 rads in 300-rad fractions) with simultaneous intrahepatic 5-fluorouracil (10-15 mg/kg/day) and intrahepatic Adriamycin 2.5-10 mg/m2/day) as part of a Phase I-II study. Of the 21 patients who completed therapy, 19 had colorectal carcinoma and 2 had metastatic adenocarcinoma of unknown origin. Objective response was judged by measurement of liver size, evaluation of liver function tests, and by liver scan or CAT scan of the liver. Ten of the 21 evaluable patients responded, yielding an overall response rate of 47.6%. The response rate in patients with colorectal carcinoma was 55% (10/19). At this time, median duration of response is 14+ weeks and median survival from onset of therapy is 15+ weeks. Hematologic and gastrointestinal toxicity were tolerable. No hepatic toxicity was documented. This combined modality therapy was found to be a safe effective method for the palliation of liver metastasis.