[(11)C]flumazenil is the reference radioligand for Positron Emission Tomography (PET) studies of central benzodiazepine (BZ) receptors. Fluorine is available in the flumazenil molecule and [(18)F]flumazenil has recently been prepared. The aim of the present PET-study in 8 male subjects was to examine the binding of [(18)F]flumazenil in the human brain by direct comparison with [(11)C]flumazenil. Each subject participated in two 93-minute PET-measurements with [(11)C]flumazenil and [(18)F]flumazenil, respectively. Data were analyzed using compartment models with metabolite-corrected arterial plasma input and reference tissue models using the pons as reference region. There was no evident difference between the kinetic behaviors of the two ligands. Overall, the noise in the time activity curves for [(18)F]flumazenil was lower at late time points, and the variance of the kinetic parameters was lower than for [(11)C]flumazenil. In BZ receptor rich regions, such as the neocortex, the 3-compartment model was statistically favored, whereas the 2-compartment model was favored in the pons. Binding potential values obtained by the reference tissue models were in good agreement with those obtained by the kinetic analysis. There was no support for the presence of specific binding in the pons. In conclusion, the binding and the kinetic behavior of [(11)C]flumazenil and [(18)F]flumazenil were similar. The present analysis supports the use of pons as reference region in simplified protocols without arterial blood sampling. [(18)F]flumazenil should thus be an excellent choice for applied studies at centers not having a cyclotron.