Continuous noninvasive monitoring of muscle oxygenation has important clinical applications for muscle disorders such as compartmentation syndrome, fibromyalgia, deep vein thrombosis, malignant hyperthermia, and the assessment of training in athletic performance. NIRS has precisely such potential and has been used to detect deep venous thrombosis, evaluate athletic performance, and assess limb reperfusion and revascularization. The aim of this study was to examine the relationship between muscle hemoglobin oxygen (HbO) and myoglobin (MbO) desaturation using NIRS combined with venous blood sampling and HbO desaturation during forearm muscle exercise. Eleven normal subjects were studied, with informed consent and an IRB-approved protocol. A NIRS sensor (INVOS4100, Somanetics, Corp.) was applied on the volar aspect of the forearm. The subjects exercised their forearm by clenching and relaxing their fist while observing the oximeter and driving the reading to specified levels from 90% to 15% (minimum possible reading). Venous blood samples were withdrawn for measurement of blood gases and oxygen saturation (IL-Co-Oximeter). RSO (%) vs VO Sat showed a two-component HbO desaturation suggesting representation of venous HbO desaturation and perhaps myoglobin oxygen (MBO) desaturation. Subtraction of the linear venous HbO curve from the two-component curve suggests MbO desaturation at venous hemoglobin oxygen saturation of about 10-20%. Conclusions: The kinetics of desaturation during exercise revealed two components representing HbO and MbO deoxygenation. The data show that MbO represents approximately 40% of the NIRS signal and the balance or 60% to HbO.