The Y chromosome-linked sex determining locus (Sry) responsible for testis determination in mammals contains a DNA-binding motif (HMG box) that is conserved across species of marsupial and placental mammals (infraclasses Metatheria and Eutheria, respectively). But little to no sequence similarity is observed in flanking sequences between these two infraclasses, or among orders within each infraclass. We investigated the rate and pattern of evolution for the coding sequence of Sry in Old World mice and rats (subfamily Murinae). We found typical rates of synonymous substitution throughout the gene, but high rates of non-synonymous substitution, especially in the C-terminal (non-HMG box) region, when compared to other genes. This region is also characterized by a frame-shift mutation and variation in a trinucleotide repeat motif. These data suggest that the non-box region is either functionally unconstrained or has undergone species-specific adaptive divergence.