Long term intracranial pressure (ICP) monitoring was carried out in over 200 patients with various intracranial abnormalities; a fiberoptic epidural intracranial pressure monitor was used. Ninety of these patients had significantly elevated ICP or exhibited pressure waves requiring therapy. Initial therapy consisted of hyperventilation with a respirator and administration of hyperosmotic agents. Comparison studies utilizing 30% urea, 20% mannitol, and furosemide intravenously and 30% urea and 10% glycerol orally were randomly done. In 45 patients two or more of these agents were used at different times in the same patient for comparison of effectiveness. When equimolar amounts of intravenous urea and mannitol were used, similar effects on increased ICP were obtained. There was no significant reduction of increased ICP with the use of furosemide alone. No rebound effect was observed with either mannitol or urea. Orally, urea was more effective than glycerol in equimolar amounts. Again no rebound was observed. In 14 patients who required doses of hyperosmotic agents more frequently than every 4 hours, continuous infusion of thiopental was used in conjunction with the hyperosmotic agents to control pressure. This regimen resulted in good ICP control in 12 patients. A rational protocol for the medical management of increased ICP utilizing hyperosmotic agents and, in refractory cases, hyperosmotic agents plus thiopental has resulted in effective control of ICP in 96% of our patients throughout their course without the need to resort to decompressive surgery. (Neurosurgery, 5: 570--575, 1979).