The aim of this study was to determine the antitumor activity of irofulven (6-hydroxymethylacylfulvene) in patients with advanced renal cell carcinoma (RCC). Eligible patients had advanced renal cell carcinoma with bidimensionally measurable disease, a Karnofsky performance status of at least 70, life expectancy of greater than three months, no prior treatment with chemotherapy, and no evidence of brain metastases. Irofulven was administered at a dose of 11 mg/m2 by 5-min intravenous infusion, on 5 consecutive days. Cycles were repeated every 28 days. Thirteen patients were enrolled in this study and 12 were evaluable for response. Of the twelve evaluable patients, no major responses were achieved. Eight patients had stable disease as best response. Toxicity included myelosuppression and gastrointestinal side effects. At the dose and schedule used in this trial, irofulven did not produce clinical response in RCC.