The ability of many investigators to carry out large-scale analyses has become more dependent on automation, including colony pickers, DNA purification robots, and capillary sequencers. We have assembled a diverse group of major users with world class credentials at Columbia University's College of Physicians & Surgeons, who have particular needs for high-throughput colony picking and sequencing. Their projects cover a wide range of cutting edge research: bacterial genome sequencing and analysis; methylation patterns in the human genome; genetic studies in yeast and bacteria; new techniques for generating full-length cDNA libraries; analysis of the T cell receptor repertoire in autoimmune diseases; genetics and molecular pharmacology of heart disease; and genome studies related to learning in Aplysia. The instruments will be housed in the Sequencing and Chemical Biology Laboratory of the Columbia Genome Center, whose investigators have substantial experience in operating these and similar pieces of equipment. A plan is described for effective sharing of the instruments among all the major users, and an Internal Advisory Committee has been formed to oversee the day-to-day operation of the instruments, and to determine rules for access by additional outside users. The Genome Center is committed to supporting these instruments over the long term, as part of its effort to provide both much needed support for faculty within and outside the Center, and in developing high-throughput methods for the eventual establishment of on-campus clinical diagnostic sequencing and mutation analysis.