The effects of Pitressin and certain stressful neurologic procedures on the human fibrinolytic system have been studied, and the role of the nervous system in fibrinolysis has been discussed. In 17 of 18 volunteers, intravenous Pitressin rapidly induced a 38 to 80% reduction in euglobulin lysis time. On 6 of 11 occasions in which the circulation of one arm was occluded prior to the injection of Pitressin into the other arm, a reduction of lysis time was noted in both arms. Pneumo-encephalography in 3 of 6 patients produced the strongest and longest lasting fibrinolytic activity thus far encountered. Of these 3 patients, 1 also had reflex-induced lytic activity appear in a cuffed arm. Marked shortening of lysis time was noted in 1 patient who fainted before a pneumoencephalogram and in another who became pale and sweaty during insertion of ventricular needles. Cerebral arteriography in 2 of 4 patients induced a moderate increase in fibrinolytic activity and, in an additional 2 patients, the needle puncture alone caused the same result. Caloric tests in 4 patients caused a brief, mild lysis, and, in 1 of these, reflexinduced fibrinolytic activity also appeared. A myelogram was without effect, and 0.6 mg of atropine given intravenously failed to prevent the enhancement of fibrinolysis by Pitressin. It appears possible that many types of peripherally and centrally induced afferent stimuli may act within the central nervous system to excite an efferent mechanism, presumably similar to the cholinergic mechanism which subserves vasodilation, to release an activator of plasminogen from vascular walls.