Hypoxia-inducible factor and physical activity Higher animals depend on an adequate oxygen flux. Mechanisms involved in the process of sensing and responding to hypoxia have become clearer in the last 15 years with the discovery of the α y β hypoxia-inducible factor (HIF) subunits and hydroxylases involved in their regulation. Reactive oxygen species seem to play some role in the process of sensing and responding to hypoxia. Skeletal muscle cells seem to be a suitable model for studying the hypoxia-reactive oxygen species HIF-cellular response relationship. Its study has important basic and clinic implications. However, the study of this relationship just begins. Some interesting aspects regarding skeletal muscle research are reviewed in this article, and some questions and hypotheses suitable for being evaluated with muscle cells are discussed.