The concentration-time profile of [14C]gabapentin (GBP) in plasma and brain interstitial fluid (ISF) was determined following a single 15 mg/kg intravenous bolus dose to rats. Brain ISF was sampled with a microdialysis probe in striatum. Blood was also collected serially to 4 h postdose. At termination, brain was sectioned into regions and [14C]GBP concentrations were determined. Anticonvulsant effects were determined by maximal electroshock in rats with identical dosing. Plasma [14C]GBP declined linearly after dosing while brain ISF [14C]GBP concentration peaked at approximately 1 h and then declined in parallel with plasma concentration. Throughout, brain ISF [14C]GBP concentration was approximately 3-6% of [14C]GBP concentration in plasma. However, at 4 h postdose, whole brain tissue [14C]GBP concentration was equal to or greater than the concentration of [14C]GBP in plasma. Maximal anticonvulsant effect lagged behind both plasma and brain ISF GBP concentrations. The anticonvulsant effect of GBP is delayed by time-dependent events other than distribution from blood to brain.