Recent concerns over the potential use of variola virus-commonly known as smallpox-and other orthopox viruses as weapons of bioterrorism have increased research efforts towards creating new antiviral drugs and safer more effective vaccines. Here we introduce a new resource for structural information of poxvirus proteins: the poxvirus proteomics database (PPDB). In the PPDB, we leverage recently developed bioinformatics structure prediction tools on a genomic scale and provide results in a publicly accessible format. The current version of the system contains both experimentally determined and predicted information about protein structural features, such as secondary structure and relative solvent accessibility, as well as tertiary structure and homology information. The system is automated to read the primary sequences from the database, produce the new information for each sequence, and update the database monthly and as new tools are incorporated. The PPDB contains detailed information on the open reading frames (ORFs) in the Copenhagen strain of the vaccinia virus genome. The contents of the PPDB can be accessed through a simple web interface. Inclusion of additional poxvirus genomes in the PPDB is in progress. The PPDB has an upward scalable informatics infrastructure that can readily be applied to viral, bacterial, as well as eukaryotic genomes.