We have investigated the antitumor effects of human lymphoblastoid interferon (HLBI) mini–pellets, interleukin–2 (IL–2) entrapped in liposome (IL–2 liposome) and an immune complex of IL–2 and monoclonal antibody against IL–2 (IC–1). The HLBI mini–pellets were administered to nude mice bearing a human renal cancer cell line (KU–2). HLBI levels remained detectable both in the tumor tissue and the serum up to 10 days after peritumor injection. The HLBI mini–pellet significantly suppressed tumor growth by peritumor administration. The antitumor effect of IL–2 liposome on Renca, a murine renal cancer, resulted in the inhibition of tumor growth. An accumulation of Lyt–2–and L3T4 lymphocytes was seen in the tumor tissue which was treated with IL–2 liposomes. The IC–1 was prepared by mixing IL–2 and anti–IL–2 monoclonal antibody at a molar ratio of 2: 1. Plasma IL–2 levels were sustained longer in mice given the IC–1 than in mice given IL–2 alone. The IC–1 complex exerted a more significant antitumor effect by local administration in Renca–bearing mice than the administration of IL–2 alone. We speculated that these effects were a result of sustained tumor IL–2 levels due to the increase in molecular weight. The results we obtained indicate that the cytokine drug delivery system has a long–acting cytotoxicity by administration to the tumor sites through efficient stimulation of the local immune response, and thus provides