Bioenergetic sufficiency can be quantitatively assayed by nuclear magnetic resonance spectroscopy (MRS) and on a relative basis by tissue optical spectroscopy (NIRS). Nuclear magnetic resonance measures quantitatively the fall of phosphocreatine and the rise of inorganic phosphate necessary to raise mitochondrial adenosine diphosphate and activate ATP synthesis to adequate level to meet metabolic demands. This relationship is readily demonstrated in skeletal muscle where the quality of supply and demand for ATP is observed over a wide range of aerobic exercise. Metabolic and genetic disease of mitochondria is readily detected by the rapid fall of PCR and rise of P_i during mild exercise and has been essential in the diagnosis and therapy of deficiency of cytochrome bc₁ in human skeletal muscle. Insufficiencies of oxygen utilization in relation to oxygen delivery are readily measured optically by the simplest of dual wavelength spectrometers. Instead of deoxygenating hemoglobin during exercise in cases of normal bioenergetic function, a luxury perfusion or hyperoxygenation of skeletal muscles occurs in exercising the energetically deficient skeletal tissue. In this way, a simple screen for metabolic and mitochondrial disease of energy production has been established and demonstrated in a number of clinical cases. Thus, the combination of the absolute evaluations by NMR and the relative indications of light of spectroscopy (NIRS) form essential tools in detection of mitochondrial defects.