31P magnetic resonance spectroscopy (MRS) was used to study an open therapeutic trial of coenzyme Q10 (CoQ) in mitochondrial encephalomyopathies. Eight patients were treated with 150 mg CoQ per day for 6 months. 31P MRS spectra of calf muscle were recorded at rest, during exercise and in the immediate postexercise recovery period. Although there was an improvement of the mean ratio of phosphocreatine (PCr) to inorganic phosphate during the post-exercise recovery period after 3 months of treatment, this finding was mainly due to a single therapy responder and did not reflect a beneficial effect on the whole group. Improved repletion of PCr persisted after 6 months of therapy. Our study identified a single responder to this therapy, whose response could not be predicted on the basis of clinical, biochemical or molecular data. These findings suggest that therapeutic trials of CoQ should be performed under close metabolic monitoring in order both to identify responders for subsequent long-term treatment and to evaluate possible mechanisms of this supportive therapy.