A simple method for the extraction of four tricyclic antidepressants from whole blood by headspace solid-phase microextraction (SPME) is presented. The whole blood samples contain four drugs (amitriptyline, chlorimipramine, imipramine, and trimipramine) and are heated at 100 degrees C in a septum-capped vial in the presence of distilled water and NaOH solution; a polydimethylsiloxane-coated SPME fiber is exposed to the headspace of the vial to allow adsorption of the drugs before capillary gas chromatography (GC) with flame-ionization detection. The headspace SPME-GC produces intense peaks for each drug with very little background noise. Recoveries of the four drugs by the present method are 5.3-12.9%. The calibration curves for the drugs show linearity in the range of 31-1000 ng/0.5 mL. The detection limits of each drug are 16-25 ng/0.5 mL. Imipramine is detectable from rat blood 5 h after oral administration of imipramine (500 mg/kg body weight); the concentration is 1.44 +/- 0.209 micrograms/mL.