The feasibility of an electrochemical detection system with on-line microdialysis coupled with sensitive microbore high-performance liquid chromatography for the measurement and brain pharmacokinetic analysis of buspirone was investigated. A microdialysis probe was inserted into the right striatum of male Sprague-Dawley rats, which had been administered buspirone (10 mg/kg, i.v.). Dialysates were automatically injected through an on-line injector into a cyano microbore column coupled to an electrochemical detector. Samples were eluted with a mobile phase containing 0.1 M monosodium dihydrogenphosphate-acetonitrile-diethylamine (85:15:0.1, v/v/v, pH 3.0, adjusted with orthophosphoric acid) at a flow-rate of 0.06 ml/min. A biphasic phenomenon with a rapid distribution phase followed by a slower elimination phase was observed from the brain buspirone concentration-time curve. The results indicate that the brain pharmacokinetics of buspirone appear to conform to a two-compartment model.