Enterotropic mouse hepatitis virus strains (MHV-RI and MHV-Y) replicate in the intestine and rarely disseminate to other tissues, unlike respiratory MHV strains. Murine carcinoembryonic antigen-related glycoproteins (MHVR and mmCGM2) are expressed in many murine tissues and serve as receptors for respiratory MHV strains. To assess the role of receptors in the limited tissue tropism of enterotropic MHV strains, the permissiveness of MHVR- and mmCGM2-expressing cell lines and peritoneal exudate cells from BALB/c and SJL mice for MHV-RI and MHV-Y replication was determined. MHVR-transfected BHK cells were susceptible to infection with both MHV-RI and MHV-Y. Additionally, the anti-MHVR monoclonal antibody CC1 blocked MHV-RI and MHV-Y infection. mmCGM2-transfected BHK cells were susceptible to infection with MHV-Y, but not MHV-RI. Peritoneal exudate cells from BALB/c mice were susceptible to infection with MHV-Y and MHV-RI, whereas peritoneal exudate cells from SJL mice were susceptible to infection with MHV-Y but not MHV-RI. These results indicate that MHV-RI probably uses a different receptor than other MHV strains to infect SJL mice and that receptors are probably not the primary determinant of the limited tissue tropism of enterotropic MHV strains.