Hypoxia occurs in most solid tumors as a result of inefficient vascular development and/or abnormal vascular architecture. During hypoxia, HIF-1alpha acts as the primary transcription factor functioning to activate multiple target genes, including vascular endothelial growth factor (VEGF). Several studies have demonstrated that in tumors HIF-1alpha mediates VEGF protein expression at the transcription level. We aimed to establish whether HCT116 colon cancer cell VEGF expression is regulated by HIF-1 levels after transient transfection with a GFP vector encoding the HIF-1alpha gene. HCT116 cell VEGF expression were therefore assayed by immunohistochemistry and ELISA. After transfection with phMGFP-HIF-1alpha, VEGF immunostaining was significantly increased in transfected cells as compared with untransfected HCT116 cells (p = 0.024, Student's t test); culture media VEGF levels assayed by ELISA were also significantly increased in transfected cells (p = 0.008, Student's t-test). These data suggest that HIF-1alpha may play an important role in colon cancer angiogenesis, both as a biomarker of metastatic potential and as a novel target for gene therapy.