Cigarette smoke condensate is a complex chemical matrix, and analysis of its components is very difficult because of the limitation of the peak capacity and sensitivity of conventional chromatography and the extensive and laborious sample preparation that is frequently required. In this study, the acidic fraction of mainstream cigarette smoke condensate has been investigated by using comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GCxGC/TOFMS). Different column systems were tested and compared under proper GCxGC/TOFMS conditions. Auto data processing by TOFMS software combined with manual identification was used to assign the components. Over 1000 compounds, with S/N > or = 100, including 139 organic acids and over 150 phenols were tentatively identified by the developed method.