Severe acute respiratory syndrome (SARS) was discovered during a recent global outbreak of atypical pneumonia. A number of immunologic and molecular studies of the clinical samples led to the conclusion that a novel coronavirus (SARS-CoV) was associated with the outbreak. Later, a SARS resequencing Gene. Chip was developed by Affymetrix to characterize the complete genome of SARS-CoV on a single Gene. Chip. The present study was carried out to evaluate the performance of SARS resequencing Gene. Chips. Two human SARS-CoV strains (CDC#200301157 and Urbani) were resequenced by the SARS Gene. Chips. Five overlapping PCR amplicons were generated for each strain and hybridized with these Gene. Chips. The successfully hybridized Gene. Chips generated nucleotide sequences of nearly complete genomes for the two SARS-CoV strains with an average call rate of 94.6%. Multiple alignments of nucleotide sequences obtained from SARS Gene. Chips and conventional sequencing revealed full concordance. Furthermore, the Gene. Chip-based analysis revealed no additional polymorphic sites. The results of this study suggest that Gene. Chip-based genome characterization is fast and reproducible. Thus, SARS resequencing Gene. Chips may be employed as an alternate tool to obtain genome sequences of SARS-CoV strains pathogenic for humans in order to further understand the transmission dynamics of these viruses.