An accurate and sensitive yet simple protocol for the analysis of toluene in submilliliter quantities of whole blood using stable-isotope dilution GC-MS has been developed and evaluated for use in pharmacokinetic studies of toluene exposure. The method involves the use of toluene-d8, a relatively inexpensive chemical used as a solvent for nuclear magnetic resonance spectroscopy, as an internal standard and extraction with pentane. This procedure allows for the determination of toluene in whole blood down to approximately 5 ng/mL and is suitable for pharmacokinetic measurements and biomonitoring of exposure to toluene.