We investigated whether the Huntington's desease (HD) gene mutation may produce either primary or secondary effects on energy metalbolism. ³¹P magnetic resonance spectroscopy demonstrated a significant decrease in the phosphocreatine to inorganic phosphate ratio in resting muscle of 8 patients as compared with 8 control subjects. The cerebrospinal fluid lactate‐pyruvate ratio was significantly increased in 15 patients as compared with 13 control subjects. Lactate concentrations assessed using ¹H magnetic resonance spectroscopy are increased in Huntington's disease cerebral cortex. Treatment with coenzyme Q₁₀, an essential cofactor of the electron transport chain, resulted in significant decreases in cortical lactate concentrations in 18 patients, which reversed following withdrawal of therapy. These findings provide evidence for a generalized energy defect in Huntington's disease, and suggest a possible therapy.