Carnitine is an essential co-factor in the catabolism of fats as an energy source. The primary purpose of this study was to investigate the effect of running a marathon on the metabolism of carnitine by endurance-trained athletes, and to evaluate the effect of carnitine administration on the performance of such exercise. The effects of marathon running on mitochondrial enzymes and cellular anti-oxidants were also examined to assess whether the expression of these activities is altered by exercise. Subjects were 10 experienced male marathon runners aged between 19 and 25 years. Running a marathon caused a fall in the plasma content of unesterified carnitine (37%) and an increase in the level of acetylcarnitine present (288%). Loading of the athletes with L-carnitine for 10 days before running a marathon abolished the exercise-induced fall in plasma-free carnitine (P less than 0.05) whilst amplifying the production of acetylcarnitine (P less than 0.05). Carnitine loading of the athletes studied made no detectable improvement in performance of the marathon (P greater than 0.05). Cytochrome oxidase, succinate cytochrome C reductase and superoxide dismutase activities present in skeletal muscle were unaltered by marathon running. However, such exercise caused a large increase in the tissue content of oxidized glutathione (189%) at the expense of reduced glutathione (-18%).