During a work designed to use MALDI-TOF MS to determine the composition of an equimolar blend of nylon 6 (Ny6) and polybutyleneterephthalate (PBT), the MALDI-TOF mass spectrum showed a surprising strong imbalance between the two components. The predominance of Ny6 oligomers over the PBT oligomers terminated with hydroxyl end chains is signaled by the appearance of specific peaks in the MALDI-TOF mass spectra. Since the average molar mass and the polydispersion of the two polymers are comparable, the MALDI-TOF MS ionization efficiency is quite different for the two components of the blend. This finding prompted us to a more detailed study, and to synthesize a number of Ny6 and PBT samples terminated with different end groups, to analyze their equimolar blends by MALDI-TOF MS. The results reported in the present study may help clarifying some fundamental aspects about the mechanisms of ions formation, when MALDI-TOF mass spectrometry is applied to macromolecules. End groups ionization efficiency appears to be the most important parameter in determining the relative intensity of peaks in the MALDI-TOF mass spectra of the polymer blends investigated. End-groups-dependent ionization of MALDI-TOF mass species is the key to rationalize the relative peak intensity in MALDI-TOF mass spectra of polymer mixtures. Understanding of ionization efficiency mechanisms is essential to the quantitative applications of MALDI-TOF MS.