There is a need for faster and more sensitive algorithms for sequence simil
arity searching in view of the rapidly increasing amounts of genomic sequen
ce data available. Parallel processing capabilities in the form of the sing
le instruction, multiple data (SIMD) technology are now available in common
microprocessors and enable a single microprocessor to perform many operati
ons in parallel. The ParAlign algorithm has been specifically designed to t
ake advantage of this technology. The new algorithm initially exploits para
llelism to perform a very rapid computation of the exact optimal ungapped a
lignment score for all diagonals in the alignment matrix. Then, a novel heu
ristic is employed to compute an approximate score of a gapped alignment by
combining the scores of several diagonals. This approximate score is used
to select the most interesting database sequences for a subsequent Smith-Wa
terman alignment, which is also parallelised, The resulting method represen
ts a substantial improvement compared to existing heuristics. The sensitivi
ty and specificity of ParAlign was found to be as good as Smith-Waterman im
plementations when the same method for computing the statistical significan
ce of the matches was used, In terms of speed, only the significantly less
sensitive NCBI BLAST 2 program was found to outperform the new approach, On
line searches are available at http://dna.uio.no/search/.