A method for the measurement of S-adenosylmethionine in cerebrospinal fluid and brain using high-performance liquid chromatography with electrochemical detection is described. The method is based upon the catechol O-methyltransferase-catalyzed methylation of dihydroxybenzylamine to its 3- and 4-methoxy derivatives and measurement of the latter. Detection limits are 0.1 pmol for 3- and 4-methoxyhydroxybenzylamine, recovery is 100%, and variability is less than 8%. HPLC measurement of 3- and 4-methoxyhydroxybenzylamine is linear up to at least 100 pmol injected. The use of a nonbiological catechol in the assay minimizes interference from endogenous and exogenous catechols and the wide limits of linearity allows the assay of small volumes of cerebrospinal fluid or brain extract without further concentration or dilution.