Cerebrospinal fluid (CSF) and plasma dopamine-beta-hydroxylase (DBH) activity was measured in 22 normotensive (NT), 31 essential hypertensive (EH), and 11 renal hypertensive (RH) patients. Although no differences were observed in their plasma DBH, the mean CSF-DBH activity and specific activity of EH were significantly lower than those of NT and RH patients. Very low CSF-DBH (less than 0.15 units/ml of CFS or less than 0.5 units/mg of CSF protein) was found only in EH (26% of EH). Of the 31 EH patients, 19(60%) had CSF-DHB activities lower than 0.5 units/ml, whereas only 5 of 22 NT (23%) and no RH fell within this range. Nevertheless, 20% of EH, 55% of NT, and 40% of RH patients had CSF-DBH activities above the mean value for NT (less than 0.9 units/ml). NT subjects with very low plasma DBH (less than 50 units/ml) had CSF-DBH activities that fell within normal range. With the exception of these subjects, the specific activity of CSF-DBH was always lower than that of the plasma enzyme. The concentration of albumin, alpha 1, beta, and gamma globulins was measured in plasma and CSF obtained from the last five NT, four EH, and two RH patients. A positive linear relationship was obtained when the log of the plasma/CSF concentration ratio for these proteins was plotted against their molecular weight. Similar slopes and intercepts were obtained for these patients, suggesting that no major differences seem to exist in their blood-brain-barrier permeability to proteins. The results suggest that measurements of CSF-DBH could be of help in the differential diagnosis of human hypertension and in the neurochemical characterization of EH. If CSF-DBH reflects central noradrenergic activity, its reduction might indicate the existence of a central catecholaminergic defect in a subgroup of EH patients.