Introduction 1 2 3 4 8 9 The rationale and effects of Bevacizumab and G250-directed therapy are fundamentally different: Bevacizumab treatment leads to VEGF-depletion and consequently to diminished neovascularization followed by tumor cell death, mainly due to loss of vascularization. In contrast, G250 treatment targets the cell surface of RCC cells where it must exert toxic effects. Both approaches have advantages and disadvantages. Bevacizumab treatment has the advantage that VEGF depletion can be achieved in the circulation, and homing to all tumor vessels is not necessary. However, other regulatory pathways can also lead to neovascularization and small, non-vascularized tumor loci will not be affected. G250 treatment has the advantage that RCC cells can be targeted, irrespective of tumor size. However, in view of the generally poor perfusion rate and high interstitial fluid pressure in RCC, deep penetration of tumors may be difficult. Also, since G250-binding alone does not confer a lytic signal to RCC cells, tumor cell kill requires effector cells or coupling of G250 to toxic agents. Bevacizumab 10 11 12 Bevacizumab in combination 13 P P 14 15 16 ® 17 ® 18 Monoclonal antibody G250 19 20 4 19 21 22 23 131 24 25 131 26 131 131 27 131 28 131 131 177 90 131 29 177 177 177 1 177 Fig. 1 left right 177  30 31 32 The largest trial, which is currently ongoing, is the adjuvant ARISER trial (adjuvant Rencarex immunotherapy phase III trial to study efficacy in nonmetastatic renal cell carcinoma). In this phase III randomized, double blind, placebo-controlled trial, patients with ECOG performance status of 0 with completely resected primary clear cell RCC and no evidence of remaining local or distant disease, are treated. The study is designed to detect a significant difference between the two treatment arms with respect to disease-free survival; patients will be followed-up long-term to determine overall survival statistics. 33 124 In conclusion, it is reasonable to assume that Bevacizumab and G250 monoclonal antibodies either as single agents or in combination with other agents may become useful additions to the armamentarium to diagnose and treat (cc)RCC. Several trials evaluating the combination of G250 or Bevacizumab with registered RCC treatments are currently in progress and will further define the role of these mAbs in RCC.