The tolerance state that exists between renal cell carcinoma (RCC) and the host's immune system would be an ideal situation in the setting of human kidney transplantation, in which graft tolerance is the ultimate goal of immunosuppressive therapy. On the other hand, acute rejection, as it appears in renal allografts, would be the optimal immunologic situation in patients with RCC. Analysis of the underlying mechanisms of acute allograft rejection and local pro-tumor immunosuppression could help to identify potential therapeutic targets for inducing immune tolerance in allograft recipients and immune rejection in RCC patients. Experimental kidney transplantation might be a suitable model in which to analyze these processes. Macrophages are a prominent and vital cell type in the cellular infiltrate seen in both RCC and renal allografts. Depending on their polarization, they can initiate and promote either proinflammatory or pro-tumor responses, which lead to tissue rejection or acceptance, respectively. Improved understanding of macrophage biology could lead to therapeutic modification of their function in order to promote a desirable immunologic response in either RCC or transplant tissue.