We describe a novel hardware architecture for genomic and proteomic sequence alignment which achieves a speed-up of two to three orders of magnitude over Smith-Waterman dynamic programming (DP) in hardware [1]-[7]. In [8, 9] we introduce several features of our search algorithm, DASH, which outperforms NCBI-Blast (BLAST) [10] by an order of magnitude in software, and has better sensitivity. Indeed, DASH has been shown to have excellent sensitivity compared to Smith-Waterman. It is designed around the principle of considering genomic and proteomic sequence alignments to typically consist of regions of high homology (the diagonals) interspersed with regions of low homology. In DASH, the optimal solution consists of such diagonals joined by regions of exact DP. This is affordable due to the small area of these inter-connecting regions, Accordingly, we have designed a chip which finds the diagonals and performs the inter-region DP directly in hardware. On a Xilinx Virtex II, XC2V6000, FPG...