We conducted a Phase II trial using an intensive regimen combining interleukin-2 (IL2), interferon-alfa-2b (IFN), and lymphokine-activated killer (LAK) cells. The aim of this study was to evaluate the toxicity and the efficacy of this combination in selected patients with metastatic renal cell carcinoma. Thirty-one assessable patients were treated with at least one cycle of a regimen consisting of 20 x 10(6) IU/day s.c. IFN for 5 days, followed 2 days later by i.v. injections of 24 x 10(6) IU/m2/day IL2 every 8 h together with i.v. bolus of 5 x 10(6) IU/m2/day IFN every 8 h during 5 days. After a 6-day break, during which four leukophereses were performed, this i.v. combination was administered along with the LAK cell reinjections for a maximum of 5 days. Twenty-seven patients underwent the two parts of the first course of treatment; respectively, 42% and 46% of the planned dose of IL2 and IFN were administered. Several severe toxicities were observed including two treatment-related deaths. Significant tumor responses were observed in seven patients, including two complete remissions. Two of these patients remain alive without evidence of disease 36 and 40 months after treatment, respectively. This intensive regimen of IL2 together with IFN and LAK cells cannot be recommended even in selected patients with metastatic renal cell carcinoma. In addition, our results argue against the concept of a dose-response relationship in this setting.