A total of 42 patients with metastatic renal cell carcinoma received floxuridine infusion for 14 days at monthly intervals. The drug was delivered via an external programmable pump on a time-modified or circadian schedule; the highest dose of 68% was given between 3 and 9 p.m. Of the 42 patients 25 (60%) had undergone prior nephrectomy. Of the 40 evaluable patients 4 (10%, 95% confidential interval 3 to 24%) achieved a partial response: 3 of the 4 had undergone prior nephrectomy, while 1 had undergone renal angioinfarction. Another 4 patients (10%) had responses at metastatic sites but no response in the primary kidney tumor. The median duration of response for these 2 groups of patients was 65 and 27 weeks, respectively, and the most responsive site was the lungs. The treatment was generally well tolerated and could be administered on an outpatient basis. Our study confirms the limited but definite activity of floxuridine infused on a circadian schedule in patients with metastatic renal cell carcinoma. We observed responses in metastasis equally in patients with or without prior nephrectomy.