AbstractTheThe Histone Database is a curated and searchable collection of full‐length sequences and structures of histones and nonhistone proteins containing histone‐like folds, compiled from major public databases. Several new histone fold‐containing proteins have been identified, including the huntingtin‐interacting protein HYPM. Additionally, based on the recent crystal structure of the Son of Sevenless protein, an interpretation of the sequence analysis of the histone fold domain is presented. The database contains an updated collection of multiple sequence alignments for the four core histones (H2A, H2B, H3, and H4) and the linker histones (H1/H5) from a total of 975 organisms. The database also contains information on the human histone gene complement and provides links to three‐dimensional structures of histone and histone fold‐containing proteins. The Histone Database is a comprehensive bioinformatics resource for the study of structure and function of histones and histone fold‐containing proteins. The database is available at http://research.nhgri.nih.gov/histones/. Proteins 2006. © 2005 Wiley‐Liss, Inc.