3-Methoxy-4-hydroxyphenylglycol (MHPG) was measured in lumbar spinal fluid of 20 subjects with hypertension of varied etiology and severity. There was a significant correlation between the concentration of MHPG and the severity of hypertension. However, changes in the concentration of vanillylmandelic acid in the urine of these subjects were insignificant. In six subjects, administration of clonidine or alpha-methyldopa, two centrally acting antihypertensive drugs, was associated with a significant lowering of MHPG concentrations. These data support the hypothesis that central catecholamines are involved in clinical hypertension.