Matrix-assisted laser desorption/ionization (LDI) mass spectrometry (MS) is a very young method that has overcome the mass limitations for the mass spectrometry of biopolymers (1 –4 ). Four years ago, a UV-absorbing matrix was used to extend the accessible mass range of UV-LDI of peptides, and a strong dependence on the UV absorption properties of the matrix was demonstrated. The mol-wt determination capability is now ca. 300,000, and since the method is still evolving, its potential is far from fully exploited. Two other mass spectrometric methods are currently applicable to high-molecular mass determination; plasma desorption mass spectrometry (Chapter 10 in this vol.) enables the production and detection of molecular ions of proteins up to about 30 kDa. Another recent technique, electrospray MS (5 ), works by spraying a solution of sample into an electric field, producing highly charged droplets, from which molecular ions are desorbed. The characteristic feature of electrospray mass spectra is a distribution of multiple-charged molecular ions, allowing mass measurement of proteins up to 70 kDa (see Chapter 8 ).