Molecular genetic studies suggest that VHL is a tumor-suppressor gene. Alterations in the von Hippel-Lindau (vHL) gene are correlated with a diverse group of neoplasms including hemangioblastoma, clear cell renal carcinoma (RCC) and pheochromocytoma. Two transcriptional elongation factors, Elongin B and C, are shown to bind in vitro and in vivo to a short, colinear region of the VHL protein (pVHL) that is frequently mutated in human tumors. It is proposed that pVHL functions in vivo as a negative regulator of transcription elongation.