The Critical Care Medicine department, St. Jans hospital, Brugge, has a prehospital emergency medicine service (EMS) staffed by experienced intensive care specialists. We have been involved in clinical research for the improvement of cerebral outcome after circulatory arrest (CA) and cardiopulmonary resuscitation (CPR) since 1977. In 1982, 250 patients in CA were resuscitated from an area of about 150,000 people. There were 70 short-term survivals, 30 longtime survivals. Although the success rate of CPR is highly influenced by important EMS related factors, including response time, a substantial proportion of hearts are restarted also after prolonged CA, but the patients die later in brain failure. There is evidence that the brain is not only damaged by the CA itself, but that lesions after restoration of spontaneous circulation (ROSC) progress and are amenable to therapy. We can illustrate the progressivity of brain lesions by two phenomena: 1) Animal experiments in other centers (P. Safar, J. Michenfelder) and our research at Janssen Pharmaceutics, Beerse, Belgium. Cerebral venous blood was sampled from the sagittal sinus after a prolonged CA (10 min); cerebral venous PO2 of 40-60 mmHg before CA, rose to 80-100 mmHg immediately after ROSC and about 1-2 h after ROSC decreased to 20-30 mmHg — indicating progressive failure of oxygen transport. 2) Cerebrospinal fluid (CSF) enzyme activity was studied after CA in humans. We correlated final neurological outcome with the early appearance (at 2k h) of lytic enzymes in the CSF. In some patients who later recover neurologically only partially, CSF enzymes are still low at 2k h, as if the cells are still viable at this stage.