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The first inborn error of creatine metabolism (guanidinoacetate methyltransferase [GAMT] deficiency) has recently been recognized in an infant with progressive extrapyramidal movement disorder. The diagnosis was established by creatine deficiency in the brain as detected by in vivo magnetic resonance spectroscopy and by defective GAMT activity and tw o mutant GAMT alleles in a liver biopsy. Here, w e describe characteristic guanidino-compound patterns in body fluids of this index patient with GAM T deficiency. Concentrations of guanidino compounds (creatine and guanidinoacetate) and creatinine w ere determined by cation-exchange chromatography and by color reaction with picric acid, respectively, in urine, plasma, and cerebrospinal fluid (CSF). Creatine concentrations w ere low in plasma, CSF, and urine w hile guanidinoacetate concentrations w ere markedly elevated. Daily urinary creatinine excretion was low, whereas creatinine concentrations in random urine samples were not always discriminative. Guanidino compound to creatinine ratios w ere not informative, as low creatinine concentrations resulted in high values for all determined compounds. During a 22-month period of oral treatment w ith creatine-monohydrate, plasma and urinary creatine concentrations increased to levels high above the normal range, and daily urinary creatinine excretion-proportional to total body creatine-became normalized. Guanidinoacetate concentrations remained elevated even during additional substitution of ornithine, which inhibits guanidinoacetate synthesis in vitro. The results indicate that GAMT deficiency can be recognized noninvasively by determination of guanidino compounds (creatine and guanidinoacetate) in body fluids. A deficiency of creatine, but not an accumulation of guanidinoacetate, can be corrected by treatment with oral creatine substitution.