OBJECTIVE Compared with mannitol, the osmotherapeutic agent sorbitol is less prone to accumulate in the blood and the same quantity may be infused in a smaller volume. Because of these advantageous characteristics, we studied the pharmacokinetics of sorbitol in serum and cerebrospinal fluid. METHODS Six patients (five women and one man; age range, 46-70 years) with an external ventriculostomy and suffering from brain edema due to cerebrovascular disease received sorbitol as part of their therapy. Before and after the first dose of 50 g infused over 20 minutes, sorbitol concentrations in serum and cerebrospinal fluid were determined repeatedly using an enzymatic procedure. RESULTS Maximal sorbitol concentrations ranged from 2,705 to 5,821 (median, 3,227) mg/l in serum compared with 6.7-130.7 (median, 19.5) mg/l in cerebrospinal fluid. Cerebrospinal fluid maxima were observed 0.17-3 hours after the end of the infusion. Sorbitol elimination in serum was adequately described by a two-compartment pharmacokinetic model (distribution half-life, 0.05-0.14 hour; elimination half-life, 0.23-0.61 hour). Elimination in cerebrospinal fluid followed a single-exponential decay and was considerably slower than that in serum (half-life, 1.3-7.7 hours). CONCLUSIONS The maximal cerebrospinal fluid concentration/maximal serum concentration ratio was low for sorbitol, thus suggesting a small potential risk of inducing an increase of intracranial pressure after osmotherapy (rebound effect).