This study concerns the development and validation of a complete method for the analysis of two highly reactive α-dicarbonyl compounds, glyoxal (Gly) and methylglyoxal (Mgly), in atmospheric fine particulate matter (PM(2.5)). Method development included optimization of sample preparation procedures, e.g., filter extraction, concentration of extracts, derivatization and solid-phase extraction (SPE) of derivatives, as well as reversed-phase liquid chromatography coupled to electrospray ion-trap mass spectrometry (HPLC-ESI-IT/MS/MS) measurement parameters. Selectivity of detection was enhanced using tandem mass spectrometric analysis in ESI positive ion mode via two multiple reaction monitoring channels, m/z 433 → m/z 250 and m/z 419 → m/z 236 for Mgly and Gly. Retention times were 9.5 and 12.5 min for Gly- and Mgly-bis-hydrazone derivatives. Calibration ranged from 0.5 to 50 ng/mL. Inter-batch precision, expressed as relative standard deviation, was <15%. The method was shown to be unaffected by the sample matrix and to have recoveries of 100% and 60% for Gly and Mgly, respectively. Improved instrumental detection limits of 0.51 and 0.62 ng/mL for Gly and Mgly were achieved using a SPE method for the purification of 2,4-dinitrophenylhydrazine derivatization reagent solutions. This permitted the method to be used for analysis of filter samples obtained during a field study at the Taunus Observatory (mount Kleiner Feldberg, Germany). PM(2.5) concentrations ranged from 0.81 to 1.18 ng/m(3) for Gly and from 0.83 to 1.92 ng/m(3) for Mgly. PM concentrations correlated to the concentration of NO with coefficients (R(2)) of 0.67 (Gly) and 0.78 (Mgly).