The second annual meeting of the NIGMS Protein Structure Initiative (PSI) research centers was held in the Natcher Conference Center on Oct. 22-23, 2001. This meeting for the nine structural genomics research centers (described at http://www.nigms.nih.gov/News/Releases/SGpilots.html and http://www.nigms.nih.gov/News/Releases/PSI2.html) focused on the bottlenecks and technical problems that are being encountered on the road to high throughput structural determination. Included were discussions of all the major tasks of structural genomics: target selection, expression, protein production, crystallization, X-ray and NMR structure determination, bioinformatics, etc. Attending were seven staff from each of the nine research centers, several speakers, and federal staff.