The relationship between MHPG concentration in several brain areas, cisternal CSF and plasma was examined in 26 vervet monkeys. Free MHPG was measured by gas chromatography-mass spectrometry using deuterated MHPG as internal standard. In animals with or without treatment with drugs that alter norepinephrine metabolism, highly significant correlations were found in concentrations of MHPG between the various brain areas, between plasma and CSF, between plasma and brain areas and between CSF and brain areas. The concentration of MHPG in CSF was higher than in plasma and with the exception of occipital cortex, all brain regions contained a higher concentration of MHPG than CSF. This study supports the notion that free MHPG concentrations in plasma and cisternal CSF are useful indices of central noradrenergic activity.