In a patient with extrapyramidal movement disorder and extremely low creatinine concentrations in serum and urine, in vivo proton magnetic resonance spectroscopy disclosed a generalized depletion of creatine in the brain. Oral substitution of arginine, a substrate for creatine synthesis, resulted in an increase of brain guanidinoacetateas the immediate precursor of creatine but did not elevate cerebral creatine levels. In contrast, oral substitution of creatine-monohydrate led to a significant increase of brain creatine, a decrease of brain guanidinoacetate, and a normalization of creatine in serum and urine. Phosphorus magnetic resonance spectroscopy of the brain revealed no detectable creatine-phosphate before oral substitution of creatine and significant increase afterward. Partial restoration of cerebral creatine concentrations was accompanied by improvement of the patient's neurologic symptoms. This is the first report of a patient with complete creatine deficiency in the brain. Magnetic resonancespectroscopy during arginine and creatine treatment point to an inborn error of creatine biosynthesis at the level of guanidinoacetate-methyltransferase.