The first part of this study investigated the combined use of furosemide and mannitol in the treatment of elevated intracranial pressure (ICP). Two groups of dogs were studied to determine if renal excretion of mannitol was altered in the presence of furosemide. No significant difference in excretion was noted between the two groups. Fifteen animals were used in other studies to identify the most advantageous sequence of administration of furosemide and mannitol. Infusion of mannitol followed by furosemide 15 minutes later resulted in the most profound and sustained ICP reduction. The effect on ICP reduction of varying the mannitol dose was observed in studies using single doses of 0.5 gm/kg, 0.75 gm/kg, and 1 gm/kg. The larger mannitol dose, resulting in a greater blood-brain osmotic gradient, proved to be the most efficacious in ICP reduction. A further 15 animals were used in investigations to determine whether changing the rate of delivery of the most effective mannitol dose (1 gm/kg) influenced resultant ICP reduction. The results indicated that rapid administration (2 ml/kg/min) produced higher peak serum concentrations of mannitol and more profound lowering of ICP than the same dose delivered at slower rates.