Funds are requested to purchase a system consisting of a Finnigan LCQ benchtop mass spectrometer and a capillary HPLC, which will be located in the Wistar Protein Microchemistry/Mass Spectrometry Core Facility. There is currently no mass spectrometer at the Wistar Institute capable of on-line MS and MS-MS analyses. The requested system will complement an existing MALDI mass spectrometer that has proven to be invaluable able for many projects, but is limited by its mass accuracy, its off- line analysis mode, and its more modest capacity to obtain MS-MS data. The requested equipment should especially improve our ability to identify and locate protein posttranslational modifications, and increase our sensitivity when identifying proteins isolated from 1D and 2D gels. The unique analytical capacities of this equipment will benefit at least 23 different laboratories at the Wistar Institute, including a major user group consists of 10 laboratories representing 9 different projects and a minor user group consisting of 13 additional laboratories. All projects involving the major user group and all minor users have NIH grant support. Any additional instrument time, not required by the identified user groups, will be made available to other researchers at the Wistar Institute, the adjacent University Of Pennsylvania, and other institutions with preference given to investigators with NIH funding. An internal advisory committee comprised of all major users and the Wistar Institute Deputy Director will oversee equitable access, operation and administration of the instrument. The Wistar Institute is committed to housing, maintaining and staffing the requested instrument for its useful lifetime as verified by an accompanying letter from the Institute's Director. The Wistar Protein Microchemistry/Mass Spectrometry Core Facility was established by Dr. Speicher in 1986. During the past five years, this core facility has been used by 183 academic laboratories including: 32 of the 40 Wistar laboratories; 81 additional users from 8 other academic institutions in the Philadelphia region; and 70 users from 32 other academic institutions outside the region.