Angiogenesis or the development of new blood vessels from the surrounding vasculature is essential for the growth and progression of solid tumors. Vascular endothelial growth factor (VEGF), a positive regulator of angiogenesis, plays a pivotal role in tumor angiogenesis and shows a high expression in almost all known tumors, including transitional cell carcinoma (TCC) of the bladder. A novel isoform, VEGF(165)b containing a novel exon 9, was recently identified in renal cell carcinoma and was shown to be down-regulated and inhibitory in nature. We aimed to analyze quantitatively expression of this isoform, VEGF(165)b, in TCC of the bladder and compare it to the benign part of the same organ. A real-time reverse transcriptase polymerase chain reaction protocol was set up to quantitate simultaneously the messenger ribonucleic acid levels of VEGF and VEGF(165)b from 34 clinical samples representing bladder cancer and matched benign tissue. Expression of VEGF(165)b showed a >or=3.0-fold change in 27 of 34 (79%) bladder tumors than the benign samples. Increased expression of VEGF(165)b was seen in superficial tumors as compared to invasive tumors, which was statistically significant (P < 0.001). Therefore, VEGF(165)b was up-regulated in TCC of the bladder.