The central neurochemistry service has continued a high level of activity in analytical methods development and analysis of human fluids and tissues. Routine analysis is presently available for MHPG, HVA, 5HIAA, 5-HT, NE and normetanephrine in plasma. These compounds as will as VMA, DOPAC, epinephrine, dopamine, metanephrine, and 3-methoxytryamine can be measured in urine. In addition, CSF measures of epinephrine, NE, DA, HVA, 5HIAA, MHPG, free and conjugated metanephrine and normetanephrine, and 5-HT are possible. New methods developed include a reverse phase HPLC procedure for separation of stable isotopes of dopamine. This will allow metabolic studies of dopamine in humans and animals without the use of GC-MS or radioactive ligands. A new assay for 5-HT in CSF was developed with limits of detection <10 pg/ml. This method takes advantage of microbore HPLC technology and a "noneluting matrix" approach to achieve the low detection limits. After studying more than 100 human samples, mean and median concentrations were found to be near the limit of detection, suggesting that CSF 5-HT is unlikely to provide insight into brain 5-HT neuronal activity. A new GC-MS assay for metanephrine and nor-metanephrine, the O-methylated metabolites of epinephrine and norepinephrine, respectively, has been developed. Conjugated and free forms of these compounds can be determined in CSF, allowing for greatly improved clinical studies on the action of MAOIs in humans.