Abstract MOTIVATION: We want to provide biologists with a fast and sensitive scanning tool for searching local alignments of a protein query sequence against databases of protein multiple alignments, such as ProDom. Conversely, we want to provide a tool for locally aligning a protein multiple alignment query against a protein database such as SWISSPROT. RESULTS: We developed the program SSMAL (Shuffling Similarities with Multiple Alignments) which utilizes features of the Blast (Altschul et al., J. Mol. Biol., 215, 403-410, 1990) algorithm and part of the Blast code. Our software allows both scanning of multiple alignments and searching with a multiple alignment. Deletions in the multiple alignment only are handled and a SSMAL search may miss some similarities found by a profile search. However, an SSMAL scan of a database such as ProDom would be 20-30 times faster that a profile scan. In the worst case, a SSMAL search is approximately 9 times faster than a profile search. AVAILABILITY: http://www.dkfz-heidelberg.de/tbi/ people/nicodeme and follow the hyperlink SSMAL. CONTACT: p.nicodeme@DKFZ-Heidelberg.de