Murine cytomegaloviruses encode a number of genes which modulate polymorpbic host immune responses. We suggest that these viral genes should themselves therefore exhibit sequence polymorphism. Additionally, clinical isolates of human cytomegalovirus (HCMV) have been shown to vary extensively from the common laboratory strains. Almost all research conducted on murine cytomegalovirus (MCMV) has used the laboratory strains Smith and K181, which have been extensively passaged in vitro and in vivo since isolation. Using the heteroduplex mobility assay (HMA) to determine levels of sequence variation 11 MCMV genes were examined from 26 isolates of MCMV from wild mice, as well as both laboratory strains. Both the HMA and sequencing of selected genes demonstrated that whilst certain genes (M33, mck-2, m147.5, m152) were highly conserved, others (m04, m06, M44, m138, m144, m145 and m155) contained significant sequence variation. Several of these genes (m06, m144 and m155) exist in wild MCMV strains as one of several distinct genotypes. (c) 2006 Elsevier Inc. All rights reserved.