Compounds, compositions and methods are provided for modulating the expression of HIF1.alpha. and/or HIF2.alpha.. The compositions comprise oligonucleotides, targeted to nucleic acid encoding HIF1.alpha. and HIF2.alpha.. Methods of using these compounds for modulation of HIF1.alpha. and/or HIF2.alpha. expression and for diagnosis and treatment of disease associated with expression of HIF1.alpha. and/or HIF2.alpha. are provided.