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Blonanserin is a novel antipsychotic agent having dopamine D(2) and serotonin 5-HT(2A) receptor antagonist properties. In this communication, a simple method for analysis of blonanserin in human plasma by gas chromatography-mass spectrometry (GC-MS) using hexobarbital as internal standard (IS) is presented. One milliliter of plasma containing blonanserin and 50 ng of IS was mixed well with 0.5 ml of 0.1 M hydrochloric acid and 2.5 ml of distilled water; the mixture was applied to an Oasis HLB cartridge. The cartridge was washed with 5 ml of distilled water, and the target compound and IS were eluted with 2 ml of chloroform. The eluate was evaporated to dryness under a stream of nitrogen. The residue was reconstituted in 50 mu l of methanol for use in GC-MS analysis. The calibration curve for blonanserin spiked into human plasma showed good linearity in the range of 0.5-20 ng/ml. The detection limit (signal-to-noise ratio = 3) was about 0.25 ng/ml. The recovery rate was 81.0% at 2.5 ng/ml and 97.5% at 15 ng/ml. The accuracy and precision were also satisfactory. A 60-year-old male volunteer took a 10-mg oral dose of blonanserin; the plasma concentrations of the drug were 0.61 and 1.20 ng/ml at 1.5 and 4 h after ingestion, respectively.