A male adult with exercise-related myalgia and weakness from the age of 17 years, developed contractions after moderate exertion which were electrically silent. Triglyceride loading or prolonged fasting provoked excessive ketosis. His isolated muscle mitochondria had severe blockade of the respiratory chain, particularly of NADH-CoQ reductase. After 1.5 years a second biopsy was performed. The electron transport capacity of the respiratory chain was much improved, but now a lesion was observed in energy transduction of sites 1 and 2 of the respiratory chain. The unexpected abolishment of respiratory chain blockade was paralleled by only mild clinical improvement.