This article describes the kinetic modeling of [(18)F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume (V(T)), specific distribution volume (V(S)), and binding potential (BP(ND)) demonstrated very good identifiability (based on coefficient of variation (COV)) for all the regions of interest (ROIs) in the gray matter (COV V(T)<7%, COV V(S)<8%, COV BP(ND)<11%). Reduction of the length of the scan to 2 hours is feasible as V(S) and V(T) showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of V(T) and V(S) was still very good with COV<10%, across high-uptake ROIs. The excellent identifiability of V(T) values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of V(T) as an appropriate and feasible outcome measure for [(18)F]-FEPPA.