The impact of elevated vascular endothelial growth factor (VEGF) expression on the course of chronic myeloid leukemia (CML) is unknown. By radioimmunoassay, we measured pretreatment cellular VEGF protein in bone marrow samples from 184 (148 chronic and 36 accelerated/blastic phases) CML patients and found the levels to be 1.6-fold higher than in 31 normal control bone marrow samples (P =.000 01). No significant differences were found in VEGF levels by different phases of CML (P =.1). VEGF levels correlated with older age (P =.01) and higher platelet count (P =.0003), but also with smaller spleen size (P =.004), lower white blood cell count (P =.0006), and lower percentage of peripheral blasts (P =.04). With the use of Cox proportional hazard model and VEGF levels as a continuous variable, high VEGF levels correlated with shorter survival of patients in chronic CML (P =.008). Multivariate analysis showed that VEGF was not independent of the synthesis stage (P =.09). These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.