The Abbott Diagnostics Amphetamine/Methamphetamine II and Amphetamine Class reagents were evaluated on the Abbott TDx for cross-reactivity to amphetamine and methamphetamine stereoisomers, several of their metabolites, and various illicit analogues, including 2-methoxyamphetamine, 4-hydroxymethamphetamine, 2,5-dimethoxy-amphetamine (DMA), 4-bromo-2,5-dimethoxyamphetamine (DOB), 4-bromo-2,5-dimethoxy-beta-phenethylamine (BDMPEA), 3,4,5-trimethoxyamphetamine (TMA), 3,4-methylenedioxy-amphetamine (MDA) N,N-dimethyl-3,4-methylenedioxy-amphetamine, N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), 2,5-dimethoxy-4-ethylamphetamine (DOE), 2,5-dimethoxy-4-methylamphetamine (DOM), and mescaline in concentrations ranging from 100 to 100,000 ng/mL. Results demonstrate the utility of this assay for detection of several of the above compounds; unfortunately many are still not detectable. Significant differences were observed between the Amphetamine/Methamphetamine II and Amphetamine Class reagents, particularly regarding their cross-reactivity to over-the-counter medications. Detection of the drugs amphetamine, methamphetamine, and the illicit analogues is not enhanced with the Amphetamine Class reagents, and unless detection of the over-the-counter compounds is of interest, these reagents are a poor choice compared to the Amphetamine/Methamphetamine II reagents. Cross-reactivity of some of the illicit analogues is such that the assay can reliably be used for the routine screening of these compounds.