We have used three different oximeters to study finger capillary SatO2, transcutaneous oxygen tension and vastus lateralis hemoglobin saturation and hemoglobin concentration in 6 volunteers under normobaric normoxia and hypobaric hypoxia. Simultaneously, the 99mTc-HMPAO uptake in the thigh muscles was assessed by planar scintigraphy. We found a highly selective uptake of 99mTc-HMPAO in the muscles of all subjects thighs. 99mTc-HMPAO uptake was significantly higher in hypoxia as compared to normoxia (p < 0.001). By comparing scintigraphy and tissue spectrophotometry (OMNIA), we observed a strong correlation between 99mTc-HMPAO uptake and hemoglobin saturation (R equals 0.96, p < 0.001) and a good correlation between 99mTc-HMPAO uptake and hemoglobin concentration (R equals 0.77, p < 0.05). These correlations indicate the occurrence of a protective vasodilatory response during hypobaric hypoxia. During hypoxia, none of the three methods used to measure oxygen saturation correlated with the actual arterial SatO2. This results suggest that different body districts react to hypoxia in a non-uniform manner. The role of the used NIRS instrumentation in assessing quantitative values needs further investigations.