MOTIVATION: The next generation sequencing technologies are generating billions of short reads daily. Resequencing and personalized medicine need much faster software to map these deep sequencing reads to a reference genome, to identify SNPs or rare transcripts. RESULTS: We present a framework for how full sensitivity mapping can be done in the most efficient way, via spaced seeds. Using the framework, we have developed software called ZOOM, which is able to map the Illumina/Solexa reads of 15x coverage of a human genome to the reference human genome in one CPU-day, allowing two mismatches, at full sensitivity. AVAILABILITY: ZOOM is freely available to non-commercial users at http://www.bioinfor.com/zoom