A method is described for simultaneous determination of cyanide (CN) and thiocyanate (SCN) in human saliva, or oral fluid. SCN concentrations in body fluids appeared to be important in classifying patients as smokers or nonsmokers, in determining some clinical conditions, and in specimen validity testing in forensic drug testing. The human saliva samples were diluted and the anions were separated by an extractive alkylation technique. Tetrabutylammonium sulfate was used as phase-transfer catalyst and pentafluorobenzyl bromide as the derivatizing agent. The products were analyzed by a gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring method. 2,5-Dibromotoluene was used as internal standard for quantitation of CN and SCN in saliva. The calibration plot was linear over the concentration range from 1 to 100 micromol/L (0.026-2.60 microg/mL) for CN (R=0.9978) and 5 to 200 micromol/L (0.29-11.6 microg/mL) for SCN (R=0.9996). The method was used to examine 10 saliva specimens. The concentration ranged from 4.8 to 29 micromol/L (0.13-0.75 microg/mL) for CN and 293 to 1029 micromol/L (17-59.7 microg/mL) for SCN. The SCN results were similar to those obtained from a method using oxidation of SCN to CN with colorimetric detection (R=0.9882). The proposed GC-MS confirmatory method was found useful when the concentrations of CN and SCN in saliva needed to be accurately determined.