The Mouse Genome Analysis Consortium used BLASTZ, an implementation of the Gapped BLAST algorithm, to align the human and mouse genomes for various purposes, particularly for studying genome evolution. BLASTZ was modified to enhance its efficiency and sensitivity for aligning entire mammalian genomes. The modifications included dynamic masking of regions with high sequence complexity and a more sensitive seeding procedure. The results showed that BLASTZ correctly aligned a significant portion of the human and mouse genomes, with a high degree of specificity. The alignment process involved several steps, including removing lineage-specific repeats, extending matches without gaps, and dynamically extending gap-free alignments. The software was tested on a cluster of 1024 833-MHz Pentium III CPUs, and the alignments were stored in a space-efficient format. The authors also developed a program, axtBest, to filter out non-orthologous alignments within a sliding window. The evaluation of BLASTZ's performance showed high specificity, with only a small fraction of alignments being spurious. The article discusses the design philosophy of BLASTZ, its implementation, and the hardware environment used for running the alignments.The Mouse Genome Analysis Consortium used BLASTZ, an implementation of the Gapped BLAST algorithm, to align the human and mouse genomes for various purposes, particularly for studying genome evolution. BLASTZ was modified to enhance its efficiency and sensitivity for aligning entire mammalian genomes. The modifications included dynamic masking of regions with high sequence complexity and a more sensitive seeding procedure. The results showed that BLASTZ correctly aligned a significant portion of the human and mouse genomes, with a high degree of specificity. The alignment process involved several steps, including removing lineage-specific repeats, extending matches without gaps, and dynamically extending gap-free alignments. The software was tested on a cluster of 1024 833-MHz Pentium III CPUs, and the alignments were stored in a space-efficient format. The authors also developed a program, axtBest, to filter out non-orthologous alignments within a sliding window. The evaluation of BLASTZ's performance showed high specificity, with only a small fraction of alignments being spurious. The article discusses the design philosophy of BLASTZ, its implementation, and the hardware environment used for running the alignments.