The activity of dopamine -hydroxylase in plasma was studied in 10 patients with various diseases accompanied by a prolonged overactivity of the sympathetic nervous system. Eight of these patients were suffering from head injury, one from tetanus and one from multiple injuries complicated by fat embolism syndrome. Plasma noradrenaline and adrenaline levels were measured concomitantly by a radioenzymatic method. It could be demonstrated that sustained increases of noradrenaline and/or adrenaline levels, which were present for several days or even weeks, were associated with a gradual decline of dopamine -hydroxylase activity. The decrease of dopamine -hydroxylase activity was more pronounced in those patients with especially high plasma catecholamine levels. In 3 patients only 13–16% of the initial dopamine -hydroxylase activity remained after an increase in the activity of the sympathetic nervous system lasting 3–4 weeks. In one of these 3 patients it could be shown that the dopamine -hydroxylase activity and the noradrenaline and adrenaline levels in plasma returned to the initial levels after complete recovery. An initial increase followed by a decline was present in these patients with the highest increases in adrenaline levels. The decline in dopamine -hydroxylase activity was not due to an increase in endogenous inhibitors, since the activity of a known amount of dopamine -hydroxylase was not reduced by adding it to a plasma in which the dopamine -hydroxylase activity was decreased.