Since the central nervous acting agent, tetramethylpyrazine, is reported to have appreciable blood-brain barrier penetrability, a design allowing simultaneous and continual monitoring of drug concentrations in blood and brain was employed to study the distribution of intravenously administered tetramethylpyrazine (10 mg kg(-1)). The system consisted of two microdialysis probes, each optimally constructed for sampling of the respective body fluids, inserted into the right jugular vein and striatum of male Sprague--Dawley rats. The probes were perfused with appropriate media at rates optimized for recovery. Dialysates were automatically collected using a microfraction collector and drugs were analyzed by high performance liquid chromatography (HPLC) with ultra violet (UV) detection. Results indicate that both blood and brain pharmacokinetics of unbound tetramethylpyrazine fit best to a two-compartment model. The elimination half-life of tetramethylpyrazine in rat blood and brain were 82.1 and 184.6 min, respectively. Increasing brain/blood concentration ratios suggested that tetramethylpyrazine effectively penetrated the blood--brain barrier.