Forty-five patients with metastatic renal cell carcinoma were treated with coumarin (1,2-benzopyrone) and cimetidine. Patients received coumarin, 100 mg orally daily; cimetidine administration, 300 mg orally four times daily, was initiated on day 15 of therapy, and treatment with both drugs was continued until progression of disease. Three patients are too early to evaluate (on study less than or equal to 2 months with no change in tumor status). Objective responses (greater than or equal to 50% reduction in measurable disease) occurred in 14 of 42 evaluable patients (33.3%) (the 95% confidence interval based on this rate is +/- 14.3%), with three complete responses and 11 partial responses (PR). Complete responses lasted 9.5, 4+, and 9.5+ months. The median duration of response for the PR group was 5 months (range, 4 to 21+ months). Twelve patients experienced stabilization of disease ranging from 4 to 16.5+ months. No response was seen in 16 patients. There was no symptomatic, hematologic, or chemical (organ dysfunction) toxicity among the 45 patients treated. Coumarin and cimetidine appear to be safe and active agents in the treatment of metastatic renal carcinoma. Further studies are required to determine the optimal dose and scheduling of these agents.