Hypoxia upregulates a number of pro-angiogenic cytokines, regulated by hypoxia-inducible factor (HIF) (Willam et al. 2002), although in vivo angiogenesis is at best modest. In response to local hypoxia we have previously demonstrated that HIF signalling may be enhanced by preventing its in situ degradation, using the peptide dimethyloxalglycine (DMOG) (Milkiewicz et al. 2004). We examined whether a similar mechanism may operate when the proximate stimulus is systemic hypoxaemia. Two groups of C57Bl6 mice (n=6 in each) were subjected to 12% normobaric hypoxia, with CO₂ scrubbing. One group received DMOG (Frontier Scientific Europe Ltd) via i.p. injection every other day (8mg in 0.5ml saline) for 14 days. Capillary growth was studied in extensor digitorum longus muscles (EDL) using fluorescein conjugated Griffonia (bandeirea) simplicifolia lectin staining of 10µm cryostat sections, to estimate changes in capillary to fibre ratio (C:F). The present study failed to demonstrate any significant angiogenesis in response to chronic environmental hypoxia. Interestingly, it also showed no effect of HIF stabilisation. Thus, systemic and local hypoxia may act differently, or have different thresholds for inducing capillary growth. As DMOG has a non-specific effect acting on many prolyl hydroxylases in a range of tissues, these data point to the requirement for more targeted pharmacological intervention to enhance angiogenesis under conditions of systemic hypoxaemia.