Six human subjects received mannitol as an intravenous dip (DIV) infusion. In each subject, the concentration of mannitol and serum osmolality were rapidly elevated during mannitol administration and reached the maximum at the end of mannitol administration. Then, it exponentially decreased. There was a strong positive correlation between mannitol concentration and extrinsic serum osmolality. The integrated values of mannitol concentration difference between the central (Cc) and the peripheral compartment (Pc) correlated with the changes of ICP reduction during mannitol administration. The results indicate that the changes of ICP reduction depend on the mannitol concentration difference between Cc and Pc.