After tumor nephrectomy, patients suffering from metastatic renal cell carcinoma (RCC) received interleukin-2 (IL-2), interferon (IFN)-alpha-2b and 5-fluorouracil (5-FU) in one to three treatment cycles over 8 weeks. Using flow cytometry, we investigated the immunophenotype of peripheral blood lymphocytes from 22 patients during therapy. In all patients, we found an increase in the absolute number of T lymphocytes, especially of the CD4 type, and in the number of HLA-DR+, CD25+ T cells and natural killer (NK) cells. The mean number of B cells did not increase during therapy. The numbers of CD4+, CD8+ and CD25+ T cells correlated significantly with the clinical response. In addition, we found that the pretherapeutic number of T lymphocytes and B cells but not of NK cells was significantly higher in patients with a therapy-induced clinical response. In conclusion, we describe the predictive value of the number of lymphocytes from peripheral blood for the efficiency of IL-2/IFN-alpha-2b therapy in combination with 5-FU in patients with metastatic renal cell carcinoma.