The nucleotide sequences of the membrane (M) protein genes and their deduced amino acid sequences of three enterotropic strains of the coronavirus mouse hepatitis virus (MHV) -Y, -RI and -DVIM were determined and compared with the previously reported sequences of two respiratory MHV strains -A59 and -JHM. The five MHV strains shared extensive nucleotide (95.2-99.0%) as well as amino acid homology (95.6-98.7%). A variable region, including a 15 nucleotide deletion unique to MHV-RI, could be identified at the 5'-terminus of the gene. This region of the M protein may be immunogenic and may contribute to the antigenic diversity of the MHV strains. Sequence relationships between the strains showed no correspondence with the primary cell tropism. This may suggest that evolution of enterotropism was not a single occurrence among different MHV strains. No sequence unique to either tropism group could be identified, indicating that the M protein of MHV probably has no part in the determination of MHV tissue tropism.