A sensitive and specific assay for the quantitative determination of amphetamine, methamphetamine and desmethyldeprenyl in human plasma specimens is described. Electron capture/negative ion chemical ionization gas chromatography/mass spectrometry is used to determine the extracted plasma concentrations of the three target compounds as their N-heptafluorobutyryl derivatives. Quantitation is performed by stable isotope dilution using d6-amphetamine and d6-methamphetamine as internal standards. Selected ion monitoring of the [M-HF]- ions of both the analytes and internal standards results in minimum quantifiable limits of 0.10 ng ml-1 for both amphetamine and methamphetamine and 0.25 ng ml-1 for desmethyldeprenyl. Excellent linearity (r = 0.998) up to at least 5.00 ng ml-1 is demonstrated.