Certain characteristic fragmentations of tryptamines (indoleethylamine) and phenethylamines are described. Based on the GC–EI/MS, LC–ESI/ MS and MALDI/TOFMS, the mass fragmentations of 13 standard compounds, including alpha-methyltryptamine (AMT), N,N-dimethyltryptamine (DMT), 5-methoxy-␣-methyltryptamine (5-MeO-AMT), N,N-diethyltryptamine (DET), N,N-dipropyltryptamine (DPT), N,N-dibutyltryptamine (DBT), N,N-diisopropyltryptamine (DIPT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), 5-methoxy-N,N-diisopropyltryptamine (5-MeODIPT), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (3,4-MDA), 3,4-methylenedioxymethamphetamine (3,4-MDMA) and 2methylamino-1-(3,4-methylenedioxyphenyl)butane (MBDB), were compared. As a result, the parent ions of these analytes were hard to be obtained by GC/MS whereas the protonated molecular ions can be observed clearly by means of ESI/MS and MALDI/TOFMS. Furthermore, two major characteristic fragmentations, namely and beta-cleavage ([M + H]+ → [3-vinylindole]+) and ␤-cleavage ([M + H]+ → [CH2N+RN1RN2]), are produced when the ESI and MALDI modes are used, respectively. In the case of ESI/MS, the fragment obtained from beta-cleavage is the major process. In contrast to this, in the case of MALDI/TOFMS, the major fragment is produced via beta-cleavage. The ionization efficiency and fragments formed from either alpha- or beta-cleavages are closely related to the degree of alkylation of the side chain nitrogen in both cases.