A relatively simple method for quantitation of amphetamine and methamphetamine in blood was developed. Blood samples were extracted with cyclohexane, and the extracts were derivatized with perfluorooctanoyl chloride prior to gas chromatography/mass spectrometry. Selected ions were monitored at m/z 118 and 440 for amphetamine, m/z 118 and 454 for methamphetamine, and m/z 121 and 443 for the internal standard amphetamine-d3. The imprecision was less than 5% for amphetamine and less than 9% for methamphetamine. Limits of detection were 11 micrograms/L for amphetamine and 13 micrograms/L for methamphetamine, while limits of quantitation were 22 and 34 micrograms/L, respectively. Calibration curves were linear in the ranges 14-2700 micrograms/L and 15-3000 micrograms/L, respectively. Some drugs that were known or suspected to interfere with immunological or chromatographic methods for amphetamine and methamphetamine were tested for interference. None of the drugs tested interfered, except for a substance in putrefied blood samples, which was found to interfere with one ion (m/z 118) for amphetamine but not with the second ion.