Adiponectin circulates in the body in high concentrations and 100-fold lower amounts were described in the cerebrospinal fluid (CSF) of mice whereas in humans contradictory results have been published. To clarify whether adiponectin is present in human CSF and is derived from the circulation it was determined in human CSF and plasma of 52 non-selected patients. Adiponectin was detected by immunoblot in CSF and was quantified in CSF and serum by ELISA. CSF adiponectin positively correlated to systemic levels and the CSF/serum adiponectin ratio correlated to the CSF/serum albumin ratio. Furthermore disturbed function of the blood-brain barrier (BBB) was associated with an elevated CSF/serum adiponectin ratio. Adiponectin mRNA was not found in the brain indicating that adiponectin crosses the BBB and/or the blood-cerebrospinal fluid barrier (BCB). Rat adiponectin with a C-terminal tag was injected into the tail vein of rats and was detected 3 h later in CSF. However, CSF adiponectin in humans and rats is approximately 0.1% of the serum concentration and therefore is below the 0.5% expected in the CSF due to the residual leakage of an undisturbed BBB/BCB. Taken together, the present study shows that adiponectin in human CSF is far below the level expected by the baseline BBB/BCB permeability, indicating that adiponectin enters the brain much less efficient than albumin thus supporting recent data that exclude adiponectin transport to the CSF. Additional studies are needed to reveal whether these low levels of adiponectin in CSF have a physiological function.