Funds are requested to purchase a DNA sequencing system consisting of an Applied Biosystems, Inc., Model 370A DNA sequencer and a Model 381A DNA synthesizer. Currently, the Seattle Biomedical Research Institute does not possess an automated DNA sequencer and all DNA sequencing is done manually. The majority of the users at the institute utilize DNA sequencing extensively in their research programs. Conversion of the manual sequencing associated with these projects to an automated DNA sequencer would result in a substantial improvement in productivity and free investigator time to be directed in new experimental directions. We currently have several long range sequencing projects such as the sequencing of a 29 kb episome or a 50 kb expression site that are only feasible with the availability of a DNA sequencer. This institute has successfully instituted a policy of providing central services to all research programs in order to improve research efficiency and to enhance its quality. The acquisition of this DNA sequencing system will greatly benefit 11 PHS funded projects and 3 pending projects. The DNA synthesizer is requested to replace our current instrument. Our current instrument is not capable of synthesizing the fluorescently labeled primers for use in the DNA synthesizer. It lacks the necessary programming/synthesis capability as well as physically lacking the extra reservoirs for the required ancillary reagents. In addition to producing fluorescently labeled primers for the DNA synthesizer, this machine will also upgrade our ability to synthesize long oligonucleotides for gene constructions as well as providing flexibility for future developments in oligonucleotide synthesis related to DNA sequencing.