Whereas cancer immunotherapy with interleukin (IL) 2 and/or other cytokines has proved effective in activating immune responses against tumor cells, the major obstacle with the use of these cytokines in cancer patients is their severe side effects when delivered systemically at high doses. In an effort to overcome this problem, in the present study, a fusion protein containing human IL-2 and a glycoinositol phospholipid (GPI) anchor sequence of decay accelerating factor was generated. When expressed by transfected cells, these fusion proteins were presented on the cell surface in the GPI-anchored form as demonstrated by fluorescence-activated cell sorter and ELISA analyses. This GPI-anchored IL-2 is highly functional as indicated by significantly increased T-cell infiltration in tumor masses. Immunohistochemical analysis of tumor cells isolated from experimental tumors indicated that a local high level of IL-2 was achieved by GPI-anchored IL-2. More importantly, when injected into mice i.v., the growth of these B16F0 melanoma cells that were engineered to express this fusion protein was significantly inhibited. In contrast, the inhibition of secreted IL-2 on tumor growth was not observable in this study. These studies may provide a novel approach to locally deliver high doses of cytokines for cancer immunotherapy.