Both the activity of lactate dehydrogenase (LDH) and the quantity of manganese superoxide dismutase (MnSOD) protein have been reported to be increased in fibroblasts from individual with mitochondrial electron transport chain defects. To ascertain whether this is a general phenomenon, we have determined the specific activities of these enzymes in skeletal muscle biopsies from control individuals and patients with defined electron transport chain defects. On investigation, both LDH and MnSOD activities were not found to be elevated. These findings suggest a possible fundamental difference between skeletal muscle preparations and fibroblasts with regard to their metabolic response to an electron transport chain defect.