Fluorouracil is a palliative antitumor agent whose use is limited by toxicity. Methods for reducing toxicity have been described, but the package insert still recommends a course of daily injections for hospital-confined patients. Such a course, in our hands, has previously resulted in severe morbidity and 14% to 16% mortality. This study compared intravenous doses of 7.5, 15, and 20 mg/kg ideal weight given undiluted at weekly intervals without a loading course to 201 patients with advanced cancer. Toxicity was mild at 7.5 mg/kg and 15 mg/kg ideal weight. It was more marked at 20 mg/kg ideal weight, and two patients died of drug toxicity. The occurrence of tumor shrinkage of more than 50% at doses of 7.5, 15, and 20 mg/kg ideal weight was 5%, 20%, and 25%, respectively. Additional patients had tumor shrinkage of less than 50% or stabilization of disease. Remissions were associated with symptomatic benefit and increased survival. A weekly intravenous injection of fluorouracil, 15 mg/kg ideal weight, without a loading course was a well-tolerated regimen that could be given safely to outpatients. Objective tumor regressions were produced as frequently on this regimen as from the currently recommended course.