A new procedure has been developed for the quantitation of aromatic amines in mainstream cigarette smoke. Two solid-phase extraction (SPE) cleanup steps using different retention mechanisms are required to process the samples. The first step uses a cation-exchange cartridge, followed by a second step that uses a cartridge with a hydrophobic retention character. The aromatic amines eluted from the second SPE cartridge are derivatized with heptafluorobutyric anhydride and analyzed with GC-MS selected ion monitoring in the negative chemical ionization mode. This new method has several advantages over other reported techniques, being sensitive, robust, and easily automated. The detection limits ranged from 0.02 ng/cigarette for tolidine to 1.41 ng/cigarette for aniline and the recoveries were from 79 to 109%.