Under Mac OS X 10.4 (Tiger) and later, bibliography files can even be searched when BibDesk is not running because the program supports Apple's Spotlight search facility. A Spotlight searchable index is automatically created whenever a file is saved within Bibdesk, and the index is updated with every save. The index is located in `~/Library/Caches/Metadata/edu.ucsd.cs.mmccrack.bibdesk' at present, but the contents of this directory must not be relied on as the file format may change in future. If the index files are deleted, they will be recreated the next time each file is saved.
Additionally, BibDesk's Spotlight search plugin adds the text of BibTeX and RIS files to the Spotlight index, but this does not allow you to identify a particular record in the files.