1H-NMR spectroscopy has been used to study metabolic perturbations in patients with disorders of propionyl-CoA metabolism during the administration of oral and intravenous L-carnitine. The administration of L-carnitine either in the form of a challenge or as a therapeutic measure resulted in an increased excretion of propionylcarnitine, consistent with the removal of accumulated intramitochondrial propionyl-CoA esters. Additionally, during the therapeutic administration of L-carnitine excretion of acetylcarnitine occurred, coincident with an improvement in clinical condition and confirming the intracellular propionyl-CoA depletion. An additional benefit from the formation of acylcarnitines may be an accompanying intracellular alkalinisation.