Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors. One such factor, vascular endothelial growth factor (VEGF), is considered to exert a potent angiogenic activity, as indicated by immunohistochemical and molecular evidence. In this study we investigated the serum VEGF level (s-VEGF) in patients with renal cell carcinoma (RCC). s-VEGF in peripheral blood samples was analyzed in 40 RCC patients and 40 patients without cancer (controls) using a sandwich enzyme-linked immunoassay. In 20 RCC patients, serum samples were obtained separately from the bilateral renal veins. s-VEGF was also measured before, 4 and 8 weeks after nephrectomy in 11 patients. There were significant differences in s-VEGF between the RCC patients and the controls (207.3+/-32.9 vs. 71.5+/-9.1 pg/ml, mean+/-SE) (P<0.005), between the tumor-bearing renal veins and the contralateral ones (P<0.01), between the pre- and post-nephrectomy situations (P<0.01) and among the various parameters of tumor status such as tumor extent (P<0.001) and existence of metastasis (P<0.001). s-VEGF significantly correlated with the tumor volume obtained by a three-dimensional measurement (r=0.802, P<0.0001). The sensitivity and specificity of s-VEGF at the cut-off level of 100 pg/ml, as determined by the receiver-operating-characteristics curve, were 80.0% and 72.5%, respectively. The results indicate that tumor tissue of RCC liberates VEGF into the systemic blood flow and that s-VEGF is a possible marker for RCC.