Matrix-assisted laser desorption/ionization (MALDI) has become an important technique for determining the molecular weights of peptides, proteins, glycoproteins, and oligonucleotides. Time-of-flight mass spectrometry (TOF-MS) is normally used with MALDI because all of the ions made by the laser pulse can be detected. Although this method is rapid and has sub- picomolar sensitivity, the mass resolution and mass measurement accuracy are limited. Recently, the applicants successfully coupled MALDI with an IonSpec externalion source Fourier transform mass spectrometer. Excellent sensitivity and ultra-high mass resolution were achieved for [Arg8]-vasopressin, neurotensin, melittin, and a number of other peptides. For bovine insulin the isotope cluster peaks were baseline resolved (M/ delta M1/2 = 90,000), and the mass measurement accuracy was 0.002 percent (20 ppm), which is more than an order of magnitude better than with TOF-MS. The sensitivity of the new MALDI-FTMS method is excellent, as demonstrated by a mass spectrum for 100 fmol of a tryptic digest of a protein. The aim of this grant application is to develop a low cost, compact FTMS instrument that can be used by non-specialists in lifescience laboratories. In Phase I, they will redesign and repackage all the electronics for the FTMS instrument. Instead of a research-grade instrument that can perform any conceivable experiment, the electronics for the new instrument will be made specifically for MALDI. Improved reliability and serviceability will be achieved by putting all the FTMS electronics in a single chassis.