Sixteen patients with metastatic renal cell carcinoma were treated with high-dose bolus recombinant interleukin-2 (rIL-2) alone at a dose and schedule identical to those that produced a 35% response rate among 72 patients in a trial reported by the Surgery Branch, National Cancer Institute (NCI), Bethesda, Md, in which rIL-2 plus lymphokine-activated killer (LAK) cells was used for the treatment of renal cell carcinoma. Patients received two 5-day cycles of 100,000 Cetus U/kg (600,000 IU/kg) of rIL-2 infused intravenously over 15 minutes every 8 hours; each treatment cycle was separated by 1 week. No objective responses were seen. The toxicity of rIL-2 given alone at these high doses was similar to that noted with high-dose rIL-2-LAK cell therapy. The lack of responses seen in this trial also differed from the 21% response rate observed by the NCI Surgery Branch, using rIL-2 alone at an identical schedule and dose in 56 patients with renal cell carcinoma. Only minor differences in such recognized prognostic variables as performance status, tumor burden, and rIL-2 dose intensity were noted between this study and other trials reported by the NCI Surgery Branch and by the IL-2-LAK Working Group. Our analysis indicates that, because of the smaller number of patients in our trial, not enough subjects were included with the ideal characteristics to attain the 21% response rate seen in the NCI study. However, the precise nature of these characteristics remains unclear.