Sensitive and accurate protein and peptide analysis remains an important feature of modern molecular biology and biomedical research. This proposal requests funds to replace our aged, but heavily used ABI 477A protein sequencer with a new ABI Procise 491 peptide sequencer. Our protein sequencing facility has seen increasing demand over the 11 years of its existence, with between 60 and 90 peptide/protein samples sequenced per year in recent years. 70-80% of these samples come from PHS-funded investigators. We currently project a continued or increasing demand for peptide sequencing services for the foreseeable future, since we have the only such service for the entire Penn State University research community (both our Medical College facility in Hershey and the larger main campus in State College, PA), and we also provide this service on a fee basis to various other smaller institutions in central Pennsylvania, including both colleges and private companies who in turn provide direct contract services to NIH. Our current lab manager has provided this service for over a decade using our current machine, and our sequencing service enjoys an excellent reputation. The Macromolecular Core is a member of the ABRF, and routinely participates in the quality assurance projects of the ABRF; the lab has performed very well in both peptide synthesis and sequencing tests over the past few years. A faculty advisory committee has been in existence for the past decade, and we have a strong institutional commitment to the success of our Core Facilities in general, and to this equipment and service specifically. Although our current machine is still functional, this is increasingly dependent on extended efforts by our lab manager to maintain the machine in working order, and we have been unofficially advised that full technical support for this machine is in its final phases. The Procise 491 requested should provide the throughput and sensitivity (many samples under 5 pmol) we need, and is likely to be more reliable during the next several years. Thus, an upgrade is both timely and necessary. The upgrading of our peptide sequencing instrumentation will enable us to continue to provide an important service in our Macromolecular Core Facility, which is a major component of the Section of Technology Development and Research Resources and is used by numerous NIH-funded investigators.