Twenty-five previously untreated patients with metastatic renal cell carcinoma were treated with 5-day cycles of continuous infusion of interleukin 2 (IL2) and lymphokine-activated killer cell reinfusion. Five achieved a partial response. Three patients were found to have detectable tumor necrosis factor (TNF) in serum before initiation of therapy. On the fifth day of therapy, 24 patients had circulating TNF with immunoradiometric assay whereas 13 had detectable biological activity. Two days after the end of IL2 therapy, TNF concentration (immunoradiometric assay) decreased in most cases but was still detectable in 17 patients. Thirteen patients had still circulating TNF bioactivity. Although there was no significant difference between TNF levels observed on the fifth day of therapy in the responder and nonresponder groups, 48 h after the end of IL2 infusion, both the TNF concentration and the biological activity were significantly higher in the group of responder patients. This result suggests that the clinical response to IL2 therapy in patients with metastatic renal cell carcinoma is correlated to a sustained production of TNF after the end of IL2 infusion.