Mouse hepatitis virus (MHV), a murine coronavirus, has been shown to utilize carcinoembryonic antigen (CEA) as the receptor. We have demonstrated that MHV can utilize a different isoform of CEA, which is an alternatively spliced gene product that is expressed in different tissues, as a receptor. Furthermore, the CEA molecules from a resistant mouse strain (SJL) have different sequences and yet serve as functional viral receptors. Thus, MHV can use more than a single type of CEA molecule as the receptor. We have also shown that some mouse cell lines express functional CEA molecules and yet are resistant to infections by certain MHV strains. Biochemical studies of the infected cells indicate that MHV infections in these cell lines are blocked at the steps of virus entry. We conclude that MHV entry requires additional cellular factors other than CEA, the viral receptor. The significance of viral receptors and the additional cellular factors in regulating viral tropism is discussed.