<jats:title>Summary</jats:title><jats:p>Concentrations of organic acids in cerebrospinal fluid (CSF) appear to be directly dependent upon their rate of production in the brain. There is evidence that the net release of short‐chain monocarboxylic acids from the brain is a major route for removing these products of cerebral metabolism. Concentrations of organic acids in blood and CSF are largely independent of each other. Quantitative reference values for the concentrations of organic acids in CSF and plasma as well as ratios of individual organic acids between CSF and plasma were determined in 35 pairs of samples from paediatric patients. Over 25 organic acids were quantifiable in all or in the majority of CSF and/or plasma specimens (limit of detection 1 µmol/L). There were substantial differences in the CSF/plasma ratios between subgroups of organic acids. Metabolites related to fatty‐acid oxidation were present in CSF in substantially less amounts than in plasma. Organic acids related to carbohydrate and energy metabolism and to amino acid degradation were present in CSF in the same amounts as or slightly smaller amounts than in plasma. Finally, some organic acids were found in substantially higher amounts in CSF than in plasma, e.g. glycolate, glycerate, 2,4‐dihydroxybutyrate, citrate and isocitrate.<jats:p>Studies of organic acids in CSF and plasma samples are presented from patients with ‘cerebral’ lactic acidosis, disorders of propionate and methylmalonate metabolism, glutaryl‐CoA dehydrogenase deficiency and<jats:sc>l</jats:sc>‐2‐hydroxyglutaric acidura. It became apparent that derangements of organic acids in the CSF may occur independently of the systemic metabolism. Quantitative organic acid analysis in CSF will yield new information on the pathophysiology in the central nervous system (CNS) of these disorders and may prove necessary for successful monitoring of treatment of organoacidopathies, which present mainly with neurological disease. For example, in glutaryl‐CoA dehydrogenase deficiency the urinary excretion of glutarate appears to be an inadequate parameter for monitoring the effect of dietary therapy, without plasma and CSF determinations. In<jats:sc>l</jats:sc>‐2‐hydroxyglutaric aciduria the elevation of<jats:sc>l</jats:sc>‐2‐hydroxyglutarate was found to be greater in CSF than in plasma. In addition, some other organic acids, glycolate, glycerate, 2,4‐dihydroxybutyrate, citrate and isocitrate, were also elevated in the CSF of the patients out of proportion to normal levels in plasma and urine. High concentrations of an unknown compound, which was tentatively identified as 2,4‐dihydroxyglutarate, were found in the CSF of patients with<jats:sc>l</jats:sc>‐2‐hydroxyglutaric aciduria. Quantitative determination of organic acids in CSF and plasma should aid the monitoring of treatment of patients with organic acid disorders, allow investigations of metabolites in known disorders, and detect neurometabolic diseases in which the diagnostic metabolites accumulate preferentially in CSF.