Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene is responsible for the development of renal carcinomas, pheochromocytomas and tumours in other organs. The gene product (pVHL) is a central component in the oxygen-sensing pathway through its role in the regulation of the hypoxia-inducible factor (HIF). Loss of pVHL leads to activation of the HIF pathway in normoxia with the concomitant increase in tumour vascularisation due to the up-regulation of pro-angiogenic genes.