Sodium valproate which seems to have an inhibitory effect on GABA-T and on succinic semialdehyde-dehydrogenase was shown to cause an increase of cerebral GABA (gamma-aminobutyric acid) concentration in animal studies [19]. The present investigations were performed to examine whether a possible influence on the cerebral GABA and dopamine metabolism and on the cyclic 3',5'-adenosine-monophosphate (cAMP) and cyclic 3',5'-guanosine-monophospnate (cGMP) system may be detectable in human beings. For this purpose the concentrations of GABA, homovanillic acid (HVA), prolactin, cAMP and cGMP were measured using OC-MS detection for GABA determination, radio-immunoassays for the measurements of cAMP, cGMP and prolactin and fluorescence detection for quantification of homovanillic acid. Before and after a three week period of treatment with valproate CSF was obtained by lumbar puncture. The results indicated a significant elevation of GABA, cAMP and homovanillic acid and a slight increase of cGMP in CSF after treatment with valproate, whereas no changes were observed in plasma prolactin, cAMP and cGMP concentrations. Thus Valproate seems to have an influence on GABA and dopamine metabolism and on the cAMP-system in man.