PARALIGN is a rapid and sensitive similarity search tool for the identification of distantly related sequences in both nucleotide and amino acid sequence databases. Two algorithms are implemented, accelerated Smith-Waterman and ParAlign. The ParAlign algorithm is similar to Smith-Waterman in sensitivity, while as quick as BLAST for protein searches. A form of parallel computing technology known as multimedia technology that is available in modern processors, but rarely used by other bioinformatics software, has been exploited to achieve the high speed. The software is also designed to run efficiently on computer clusters using the message-passing interface standard. A public search service powered by a large computer cluster has been set-up and is freely available at www.paralign.org, where the major public databases can be searched. The software can also be downloaded free of charge for academic use.