The R (replicase) protein is the uniquely defined non-structural protein (NSP)responsible for RNA replication, mutation rate or fidelity, regulation of transcrip-tion in coronaviruses and many other ssRNA viruses. Based on our completegenome sequences of four isolates (BJ01-BJ04) of SARS-CoV from Beijing, China,we analyzed the structure and predicted functions of the R protein in comparisonwith 13 other isolates of SARS-CoV and 6 other coronaviruses. The entire ORF(open-reading frame) encodes for two major enzyme activities, RNA-dependentRNA polymerase (RdRp) and proteinase activities. The R polyprotein under-goes a complex proteolytic process to produce 15 function-related peptides. Ahydrophobic domain (HOD) and a hydrophilic domain (HID) are newly identifiedwithin NSP1. The substitution rate of the R protein is close to the average ofthe SARS-CoV genome. The functional domains in all NSPs of the R proteingive different phylogenetic results that suggest their different mutation rate underselective pressure. Eleven highly conserved regions in RdRp and twelve cleavagesites by 3CLP (chymotrypsin-like protein) have been identified as potential drugtargets. Findings suggest that it is possible to obtain information about the phy-logeny of SARS-CoV, as well as potential tools for drug design, genotyping anddiagnostics of SARS.