Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows detection of large molecules such as those present in synthetic and natural macromolecules. Until recently, it was reported that MALDI-TOF measurements can provide correct molecular weight (MW) estimates only for nearly monodisperse polymer samples. We have now developed a methodology for polydisperse samples. We recorded the gel-permeation chromatography (GPC) trace of a polydisperse polymeric sample of poly(dimethylsiloxane) (PDMS), collecting 42 fractions. Selected fractions were analyzed by MALDI-TOF and the average MW of each fraction was determined, allowing a calibration of GPC curves against absolute MW. The calibrated GPC trace was then used to compute average MW and molecular-weight distribution (MWD) of the unfractionated poly(dimethylsiloxane) sample. In the spectra of low molecular-weight fractions, the resolution is high enough to resolve the contributions of the various PDMS oligomers as separate signals.