The first Phase I Trial with a combination of IL-2 and IFN-alpha was published in 1989. There are still some questions though, concerning the in vivo effects of this combination on lymphocytes. We designed a prospective pilot study to evaluate in vivo effects of low dose IL-2 and IFN-alpha combination on expression of Bcl-2, FAS (Apo-1/CD 95), Fas Ligand, IL-2 receptor (CD25), and HLA-DR on peripheral lymphocytes in patients with advanced renal cell carcinoma. After initiation of the immunomodulating therapy, Bcl-2 expressing lymphocytes increased significantly on day 3 (p < 0.025), Fas (Apo-1/CD95) expressing lymphocyte increased significantly on day 5 (p < 0.003), Fas ligand expressing lymphocytes increased significantly on day 3 (p < 0.004), HLA-DR expressing lymphocytes increased significantly on day 5 (p < 0.003), and IL-2 receptor (CD25) expressing cells increased significantly on day 5 (p < 0.01). We conclude that immunomodulating therapy induces in vivo expression of Bcl-2, Fas (Apo-1) and Fas Ligand in lymphocytes significantly.