Inhibition of autocrine VEGFR-1 pathways reduces growth of established lymphoma xenografts in NOD/SCID mice and correlates with increased tumor apoptosis. Sublethally irradiated NOD/SCID mice were engrafted with subcutaneous RL lymphoma xenografts and were treated by intraperitoneal injection 3 times weekly with human immunoglobulin (IVIG), anti–human VEGFR-1 (6.12), or anti–murine VEGFR-2 (MF-1) antibodies. (A) Mean tumor volumes (± SE) are shown for experimental groups of 5 to 10 mice. Results were statistically significant (P < .05) for IVIG compared with 6.12 on days 2 to 19. (B) Immunohistochemical staining of xenografts following treatment demonstrated increased tumor apoptosis after VEGFR-1 (6.12) treatment compared with controls (BV = blood vessels). Inset shows TUNEL+ apoptotic lymphoma cells at 40 × magnification. (C) Quantification of the mean number of TUNEL+ cells (± SE) per low-power field (10 ×) in treated xenografts is shown (P < .05).