OBJECTIVE Treatment of patients with metastatic renal cell carcinoma with high-dose interleukin-2 (IL-2) administered as continuous intravenous (CIV) infusion or as bolus injection results in response rates of 15% to 30%; however, toxicities with these regimens have been severe. A trial in which CIV IL-2 was administered at high doses during days 1 to 5 and at reduced doses during days 10 to 20 reported less toxicity without a decrease in response rates. We treated a series of patients with this regimen and our experience is presented. METHODS Seventeen patients with metastatic renal cell carcinoma were treated with IL-2 by CIV at a dose of 18 x 10(6) IU/m2/day for 5 days followed by 4 to 6 days of rest followed by 10 days of CIV IL-2 at a dose of 6 x 10(6) IU/m2/day. Five patients also received CT-1501R, a pentoxifylline derivative. RESULTS There was 1 partial responder (PR) and there were no complete responses. The patient with the PR had a 14 x 9 cm(2) renal tumor with metastases to lung, pancreas, and liver. A surgical resection induced a CR, but he relapsed 9 months later. Severe toxicities included hyponatremia (serum sodium of less than 123 mmol/L) (n=3), biopsy-proven cardiomyopathy (n=1), creatinine more than 4.5 mg/dL (n=7), and sudden death (n=1). CONCLUSIONS We conclude that high-dose CIV IL-2 therapy of renal cell carcinoma results in severe toxicity and cannot be recommended for general use. Alternatives need to be developed.